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Vaccines, Volume 9, Issue 11 (November 2021) – 164 articles

Cover Story (view full-size image): Dual vaccines were developed against two debilitating cattle viruses, lumpy skin disease virus (LSDV) and bovine ephemeral fever virus (BEFV). Because the infections are seasonal and sporadic, vaccine uptake is poor. A single vaccine targeting the two viruses would be cost effective and improve vaccine coverage against both viruses, which co-localize geographically, largely in Africa. Two modified LSDV backbones were tested, both as vaccine (against LSDV) and vector (for BEFV). The BEFV glycoprotein and matrix genes were inserted into the LSDV backbones, and the candidate vaccines were tested in cattle. After two vaccinations, all animals elicited both neutralizing and binding antibodies against BEFV. All vaccinated animals developed both neutralizing and T cell responses against LSDV and were protected against virulent LSDV challenge. View this paper
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Article
Development of a Candidate Multi-Epitope Subunit Vaccine against Klebsiella aerogenes: Subtractive Proteomics and Immuno-Informatics Approach
Vaccines 2021, 9(11), 1373; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111373 - 22 Nov 2021
Viewed by 394
Abstract
Klebsiella aerogenes is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, [...] Read more.
Klebsiella aerogenes is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, which confer high resistance. The drug resistance in K. aerogenes has been reported in China, Israel, Poland, Italy and the United States, with a high mortality rate (~50%). This study aims to combine immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against K. aerogenes. The synthesis of the B-cell, T-cell (CTL and HTL) and IFN-γ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies. The vaccine was predicted by connecting the respective epitopes, i.e., B cells, CTL and HTL with KK, AAY and GPGPG linkers and all these were connected with N-terminal adjuvants with EAAAK linker. The humoral response of the constructed vaccine was measured through IFN-γ and B-cell epitopes. Before being used as vaccine candidate, all identified B-cell, HTL and CTL epitopes were tested for antigenicity, allergenicity and toxicity to check the safety profiles of our vaccine. To find out the compatibility of constructed vaccine with receptors, MHC-I, followed by MHC-II and TLR4 receptors, was docked with the vaccine. Lastly, in order to precisely certify the proper expression and integrity of our construct, in silico cloning was carried out. Further studies are needed to confirm the safety features and immunogenicity of the vaccine. Full article
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Article
Patients’ Perception and Knowledge about Influenza and Pneumococcal Vaccination during the COVID-19 Pandemic: An Online Survey in Patients at Risk of Infections
Vaccines 2021, 9(11), 1372; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111372 - 22 Nov 2021
Viewed by 407
Abstract
Introduction: The objective of our study was to assess, in an at-risk population, perception and knowledge about influenza and pneumococcal vaccinations. Methods: An anonymous web-based survey was submitted to patients recruited in France, from both an Ipsos internal panel and AVNIR patient associations. [...] Read more.
Introduction: The objective of our study was to assess, in an at-risk population, perception and knowledge about influenza and pneumococcal vaccinations. Methods: An anonymous web-based survey was submitted to patients recruited in France, from both an Ipsos internal panel and AVNIR patient associations. The study was conducted between July and October 2020, in the context of the COVID-19 pandemic. Results: Overall, 2177 questionnaires from patients at risk of infection were analyzed. Almost all respondents (86%, 1869/2177) declared themselves to be favorable to vaccination. Nearly half of the patients (49%, 1069/2177) were aware of which vaccine was recommended for their specific situation. This percentage was significantly (p < 0.001) higher for members of a patient association and for people affected by multiple chronic conditions and varied according to the type of condition. Almost two-thirds of patients (1373/2177) declared having been vaccinated during the 2019/2020 influenza season, and 41% (894/2177) were certain about being up to date with the pneumococcal vaccination. The main barriers to vaccination for influenza are the fear of side effects, doubt regarding the efficacy of the vaccine and for pneumococcal vaccination, and the absence of suggestions by the healthcare professionals (HCPs), as 64% of respondents were not recommended to obtain pneumococcal vaccination. To improve vaccine coverage, information is of prime importance and GPs are recognized as the main HCP to inform about vaccination. Nearly two-thirds (62%, 1360/2177) of patients declared that the COVID-19 pandemic convinced them to have all the recommended vaccines. Conclusion: Our study highlighted the nonoptimal vaccine coverage in at-risk populations despite a highly positive perception of vaccines and confirmed that physicians are on the front lines to suggest and recommend these vaccinations, especially in the current pandemic context, which may be used to promote other vaccines. Full article
(This article belongs to the Section Epidemiology)
Article
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β
Vaccines 2021, 9(11), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111371 - 22 Nov 2021
Viewed by 521
Abstract
African swine fever virus (ASFV) poses serious threats to the swine industry. The mortality rate of African swine fever (ASF) is 100%, and there is no effective vaccine currently available. Complex immune escape strategies of ASFV are crucial factors affecting immune prevention and [...] Read more.
African swine fever virus (ASFV) poses serious threats to the swine industry. The mortality rate of African swine fever (ASF) is 100%, and there is no effective vaccine currently available. Complex immune escape strategies of ASFV are crucial factors affecting immune prevention and vaccine development. CD2v and MGF360-505R genes have been implicated in the modulation of the immune response. The molecular mechanisms contributing to innate immunity are poorly understood. In this study, we discover the cytopathic effect and apoptosis of ΔCD2v/ΔMGF360-505R-ASFV after infection in porcine alveolar macrophages (PAMs) was significantly less than wild-type ASFV. We demonstrated that CD2v- and MGF360-505R-deficient ASFV decrease the level of apoptosis by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription. Compared with wild-type ASFV infection, the levels of phospho-NF-κB p65 and p-IκB protein decreased in CD2v- and MGF360-505R-deficient ASFV. Moreover, CD2v- and MGF360-505R-deficient ASFV induced less IL-1β production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. We further found that MGF360-12L, MGF360-13L, and MGF-505-2R suppress the promoter activity of NF-κB by reporter assays, and CD2v activates the NF-κB signaling pathway. These findings suggested that CD2v- and MGF360-505R-deficient ASFV could reduce the level of ASFV p30 and the apoptosis of PAMs by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription, which might reveal a novel strategy for ASFV to maintain the replication of the virus in the host. Full article
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Article
Deciphering the Molecular Basis for Attenuation of Flavobacterium columnare Strain Fc1723 Used as Modified Live Vaccine against Columnaris Disease
Vaccines 2021, 9(11), 1370; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111370 - 22 Nov 2021
Viewed by 387
Abstract
Vaccines are widely employed in aquaculture to prevent bacterial infections, but their use by the U.S. catfish industry is very limited. One of the main diseases affecting catfish aquaculture is columnaris disease, caused by the bacterial pathogen Flavobacterium columnare. In 2011, a [...] Read more.
Vaccines are widely employed in aquaculture to prevent bacterial infections, but their use by the U.S. catfish industry is very limited. One of the main diseases affecting catfish aquaculture is columnaris disease, caused by the bacterial pathogen Flavobacterium columnare. In 2011, a modified-live vaccine against columnaris disease was developed by selecting mutants that were resistant to rifampin. The previous study has suggested that this vaccine is stable, safe, and effective, but the mechanisms that resulted in attenuation remained uncharacterized. To understand the molecular basis for attenuation, a comparative genomic analysis was conducted to identify specific point mutations. The PacBio RS long-read sequencing platform was used to obtain draft genomes of the mutant attenuated strain (Fc1723) and the parent virulent strain (FcB27). Sequence-based genome comparison identified 16 single nucleotide polymorphisms (SNP) unique to the mutant. Genes that contained mutations were involved in rifampin resistance, gliding motility, DNA transcription, toxin secretion, and extracellular protease synthesis. The results also found that the vaccine strain formed biofilm at a significantly lower rate than the parent strain. These observations suggested that the rifampin-resistant phenotype and the associated attenuation of the vaccine strain result from the altered activity of RNA polymerase (RpoB) and possible disrupted protein secretion systems. Full article
(This article belongs to the Special Issue Vaccines for Aquaculture)
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Article
Unfolding the Mild to Moderate Short-Term Side Effects of Four COVID-19 Vaccines Used in Bahrain: A Cross-Sectional Study
Vaccines 2021, 9(11), 1369; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111369 - 22 Nov 2021
Viewed by 567
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) created a global pandemic (COVID-19) that has resulted in massive health and economic losses. The current unavailability of treatments leaves vaccination as the only way to control this disease. There are four vaccines (Sinopharm, Pfizer—BioNTech, Sputnik, [...] Read more.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) created a global pandemic (COVID-19) that has resulted in massive health and economic losses. The current unavailability of treatments leaves vaccination as the only way to control this disease. There are four vaccines (Sinopharm, Pfizer—BioNTech, Sputnik, and AstraZeneca) available in Bahrain. This project aimed to study the most common side effects resulting from the first and second doses of these four vaccines. Data were collected through an online questionnaire answered by 311 individuals who received both doses of one of these four vaccines. The results of this study revealed that regardless of the vaccine identity, participants experienced more side effects from the second dose. Among the different side effects, pain at the site of injection was primarily observed after the first dose of the Pfizer vaccine (43%), which was followed by the AstraZeneca vaccine (31%). Moreover, fever was observed in participants after the first dose of the Sputnik vaccine (37%), while headache was mainly observed after the first dose of the Pfizer vaccine (32%). It is important to note that fatigue was observed after the first dose of all four vaccines but was reported by the highest proportion of respondents in the Pfizer group (28%). Interestingly, there are some side effects, such as pain at the site of injection, that are correlated with fever (r = 0.909). Similarly, headache is correlated with fever (r = 0.801) and pain at the site of injection (r = 0.868). Overall, it was observed that recipients of the Sinopharm vaccine reported the mildest side effects among all four vaccines. The crucial finding of this study is that the first and second dosage post-vaccination side effects were modest and predictable with no occurrences of hospitalization; this information can assist in lessening vaccine apprehension. Full article
(This article belongs to the Collection COVID-19 Vaccines and Vaccination)
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Article
The Cost-Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine in Seven Chinese Cities
Vaccines 2021, 9(11), 1368; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111368 - 20 Nov 2021
Viewed by 497
Abstract
Objective: This study estimates the cost-effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) among infants in Beijing, Shanghai, Shenzhen, Chengdu, Karamay, Qingdao, and Suzhou. Methods: A previously published cost-effectiveness model comparing vaccination with PCV13 to no vaccination was localized to the [...] Read more.
Objective: This study estimates the cost-effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) among infants in Beijing, Shanghai, Shenzhen, Chengdu, Karamay, Qingdao, and Suzhou. Methods: A previously published cost-effectiveness model comparing vaccination with PCV13 to no vaccination was localized to the included Chinese cities. A systematic literature review was undertaken to identify age-specific incidence rates for pneumococcal bacteremia, pneumococcal meningitis, pneumonia, and otitis media (AOM). Age-specific direct medical costs of treating the included pneumococcal diseases were taken from the Chinese Health Insurance Association database. The base case analysis evaluated vaccine efficacy using direct effect and indirect effects (DE+ IDE). A subsequent scenario analysis evaluated the model outcomes if only DE was considered. A vaccination rate of 70% was used. The model reported outcomes over a one-year period after it was assumed the vaccine effects had reached a steady state (5–7 years after vaccine introduction) to include the direct and indirect effects of vaccination. Health outcomes were discounted at 5% during the steady-state period. Results: Vaccination with PCV13 was cost-effective in the base case analysis for all included cities with the incremental cost-effectiveness ratio (ICER) ranging from 1145 CNY(Shenzhen) to 15,422 CNY (Qingdao) per quality-adjusted life-year (QALY) gained. PCV13 was the dominant strategy in Shanghai with lower incremental costs and higher incremental QALYs. PCV13 remained cost-effective in the DE-only analysis with all ICERs falling below a cost-effectiveness threshold of three times GDP per capita in each city. Conclusions: Vaccination with PCV13 was a cost-effective strategy in the analyzed cities for both the DE-only and DE + IDE analyses. PCV13 became very cost-effective when a vaccination rate was reached where IDE is observed. Full article
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Article
Anti-Spike SARS-CoV-2 IgG Assessment with a Commercial Assay during a 4-Month Course after COVID-19 Vaccination
Vaccines 2021, 9(11), 1367; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111367 - 20 Nov 2021
Viewed by 575
Abstract
We intended to assess the humoral response induced by the Pfizer/BioNTech Comirnaty COVID-19 vaccine with commercially available immunoassays: anti-spike (S) IgG and IgM, and anti-nucleocapsid (N) IgG antibodies, over a 4-month course. One hundred subjects, including 15 COVID-19 convalescents, comprised the study cohort. [...] Read more.
We intended to assess the humoral response induced by the Pfizer/BioNTech Comirnaty COVID-19 vaccine with commercially available immunoassays: anti-spike (S) IgG and IgM, and anti-nucleocapsid (N) IgG antibodies, over a 4-month course. One hundred subjects, including 15 COVID-19 convalescents, comprised the study cohort. The SARS-CoV-2 antibodies concentrations were measured on day 0′ and 10′, 20′, 30′, 60′, 90′, and 120′ after the first dose administration. Over the course of the study, 100% of the participants developed and sustained anti-SARS-CoV-2 S IgG antibodies. The highest concentration, exceeding the quantification range of the test (2080 BAU/mL), was reached by 67% of the subjects on day 30′. The concentration of the antibodies remained stable between days 30′ and 90′ but was followed by a significant decrease between days 90′ and 120′. The stronger and more persistent humoral response was noted for women. The COVID-19 convalescents developed higher antibody levels, particularly 10 days after the first Comirnaty dose. Twenty-three out of the eighty-five naïve vaccinees failed to develop a detectable IgM response. LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin S.p.A, Saluggia, Italy) may be useful in the assessment of the humoral response to the Comirnaty vaccine. In contrast, Abbott’s anti-S SARS-CoV-2 IgM has a limited utility in this context. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Article
Vaccinating against COVID-19: The Correlation between Pro-Vaccination Attitudes and the Belief That Our Peers Want to Get Vaccinated
Vaccines 2021, 9(11), 1366; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111366 - 20 Nov 2021
Viewed by 1087
Abstract
This study verifies whether there is a strong correlation between the pro-vaccination, against COVID-19 attitude of the respondents and their belief that most of those around them want to be vaccinated against COVID-19. For this purpose, we analyzed data from a sociological survey [...] Read more.
This study verifies whether there is a strong correlation between the pro-vaccination, against COVID-19 attitude of the respondents and their belief that most of those around them want to be vaccinated against COVID-19. For this purpose, we analyzed data from a sociological survey conducted in April 2021 in Romania. The sample size was of 1001 respondents, the selection process was randomized and the population included in the sample is representative of the socio-demographic structure of Romania. The tool used to collect the data was CATI (telephonic interview). In order to test the existence of these correlations we performed the following tests: Chi-Square test, Kendall τ, Spearman ρ tests and Freeman’s z-test. The pro-vaccination attitude strongly correlates with the perception of subjects that their primary group accepts vaccination and even correlates with the perception that the general public is rather pro-vaccination. The vaccination decision is closely linked to the social relations system and the rules of the community in which the subject lives. In this paper we discuss the correlation between attitude and belief, not the existence of a causal relation between the two of them. Full article
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Article
SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
Vaccines 2021, 9(11), 1365; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111365 - 20 Nov 2021
Cited by 1 | Viewed by 601
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute respiratory distress syndrome. In this study, we explored the feasibility of using plants to produce an anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) and examined its utility in reducing IL-6 signaling in an in vitro model, which simulates IL-6 induction during SARS-CoV-2 infection. The anti-IL6R mAb (IL6RmAb) was quickly expressed and correctly assembled in Nicotiana benthamiana leaves. Plant-produced IL6RmAb (pIL6RmAb) could be enriched to homogeneity by a simple purification scheme. Furthermore, pIL6RmAb was shown to effectively inhibit IL-6 signaling in a cell-based model system. Notably, pIL6RmAb also suppressed IL-6 signaling that was induced by the exposure of human peripheral blood mononuclear cells to the spike protein of SARS-CoV-2. This is the first report of a plant-made anti-IL-6R mAb and its activity against SARS-CoV-2-related cytokine signaling. This study demonstrates the capacity of plants for producing functionally active mAbs that block cytokine signaling and implies their potential efficacy to curb cytokine storm in COVID-19 patients. Full article
(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)
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Article
Regional Differences in COVID-19 Vaccine Hesitancy in December 2020: A Natural Experiment in the French Working-Age Population
Vaccines 2021, 9(11), 1364; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111364 - 20 Nov 2021
Viewed by 576
Abstract
It can be assumed that higher SARS-CoV-2 infection risk is associated with higher COVID-19 vaccination intentions, although evidence is scarce. In this large and representative survey of 6007 adults aged 18–64 years and residing in France, 8.1% (95% CI, 7.5–8.8) reported a prior [...] Read more.
It can be assumed that higher SARS-CoV-2 infection risk is associated with higher COVID-19 vaccination intentions, although evidence is scarce. In this large and representative survey of 6007 adults aged 18–64 years and residing in France, 8.1% (95% CI, 7.5–8.8) reported a prior SARS-CoV-2 infection in December 2020, with regional variations according to an East–West gradient (p < 0.0001). In participants without prior SARS-CoV-2 infection, COVID-19 vaccine hesitancy was substantial, including 41.3% (95% CI, 39.8–42.8) outright refusal of COVID-19 vaccination. Taking into account five characteristics of the first approved vaccines (efficacy, duration of immunity, safety, country of the vaccine manufacturer, and place of administration) as well as the initial setting of the mass vaccination campaign in France, COVID-19 vaccine acceptance would reach 43.6% (95% CI, 43.0–44.1) at best among working-age adults without prior SARS-CoV-2 infection. COVID-19 vaccine acceptance was primarily driven by vaccine characteristics, sociodemographic and attitudinal factors. Considering the region of residency as a proxy of the likelihood of getting infected, our study findings do not support the assumption that SARS-CoV-2 infection risk is associated with COVID-19 vaccine acceptance. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Review
The Advantages and Challenges of Anticancer Dendritic Cell Vaccines and NK Cells in Adoptive Cell Immunotherapy
Vaccines 2021, 9(11), 1363; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111363 - 19 Nov 2021
Viewed by 586
Abstract
In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has improved therapeutic potential and significant value in promising cancer treatment for patients. The ACT is based on the cell transfer of dendritic cells (DCs) and/or immune effector [...] Read more.
In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has improved therapeutic potential and significant value in promising cancer treatment for patients. The ACT is based on the cell transfer of dendritic cells (DCs) and/or immune effector cells. DCs are often used as vaccine carriers or antigen-presenting cells (APCs) to prime naive T cells ex vivo or in vivo. Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are used as major tool effector cells for ACT. Despite the fact that NK cell immunotherapy is highly effective and promising against many cancer types, there are still some limitations, including insignificant infiltration, adverse conditions of the microenvironment, the immunosuppressive cellular populations, and the low cytotoxic activity in solid tumors. To overcome these difficulties, novel methods of NK cell isolation, expansion, and stimulation of cytotoxic activity should be designed. In this review, we discuss the basic characteristics of DC vaccines and NK cells as potential adoptive cell preparations in cancer therapy. Full article
(This article belongs to the Special Issue Cell-Mediated Immunity and Cancer Vaccines)
Article
A Community-Based Management of COVID-19 in a Mobile Container Unit
Vaccines 2021, 9(11), 1362; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111362 - 19 Nov 2021
Viewed by 608
Abstract
Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved [...] Read more.
Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally. Full article
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Article
Validation of Pretreatment Methods for the In-Process Quantification of Foot-and-Mouth Disease Vaccine Antigens
Vaccines 2021, 9(11), 1361; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111361 - 19 Nov 2021
Viewed by 424
Abstract
Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is controlled by vaccine policy in many countries. For vaccine potency, the content of intact virus particles (146S antigens) is critical, and the sucrose density gradient (SDG) fractionation is the gold standard for the [...] Read more.
Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is controlled by vaccine policy in many countries. For vaccine potency, the content of intact virus particles (146S antigens) is critical, and the sucrose density gradient (SDG) fractionation is the gold standard for the quantification of 146S antigens. However, this method has several drawbacks. Although size-exclusion high-performance liquid chromatography (SE-HPLC) was introduced to replace the classic method, its application is generally confined to purified samples owing to the interfering signals. Therefore, we aimed to develop optimal pretreatment methods for SE-HPLC quantification in less purified samples. Crude virus infection supernatant (CVIS) and semi-purified samples with PEG precipitation (PEG-P) were used. Chloroform pretreatment was essential to remove a high level of non-specific signals in CVIS, whereas it caused loss of 146S antigens without the distinctive removal of non-specific signals in PEG-P. Benzonase pretreatment was required to improve the resolution of the target peak in the chromatogram for both CVIS and PEG-P. Through spiking tests with pure 146S antigens, it was verified that the combined pretreatment with chloroform and benzonase was optimal for the CVIS, while the sole pretreatment of benzonase was beneficial for PEG-P. Full article
(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)
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Systematic Review
Pharmacists’ Perceived Barriers to Human Papillomavirus (HPV) Vaccination: A Systematic Literature Review
Vaccines 2021, 9(11), 1360; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111360 - 19 Nov 2021
Viewed by 457
Abstract
About 45:000 cancers are linked to HPV each year in the United States alone. The HPV vaccine prevents cancer and is highly effective, yet vaccination coverage remains low. Pharmacies can play a meaningful role in increasing HPV vaccination access due to their availability [...] Read more.
About 45:000 cancers are linked to HPV each year in the United States alone. The HPV vaccine prevents cancer and is highly effective, yet vaccination coverage remains low. Pharmacies can play a meaningful role in increasing HPV vaccination access due to their availability and convenience. However, little is known about pharmacists’ perceived barriers to HPV vaccination. The objective of this systematic review was to summarize existing literature on perceived barriers to administering HPV vaccination reported by pharmacists. Barriers identified from selected studies were synthesized and further grouped into patient, parental, (pharmacist’s) personal, and system/organization barrier groups. Six studies were included in this review. The cost of the HPV vaccine, insurance coverage and reimbursement were commonly reported perceived barriers. Adolescent HPV vaccination barriers related to parental concerns, beliefs, and inadequate knowledge about the HPV vaccine. Perceived (pharmacist’s) personal barriers were related to lack of information and knowledge about HPV vaccine and recommendations. At the system/organization level, barriers reported included lack of time/staff/space; difficulty in series completion; tracking and recall of patient; perceived competition with providers; and other responsibilities/vaccines taking precedence. Future strategies involving pharmacy settings in HPV-related cancer prevention efforts should consider research on multilevel pharmacy-driven interventions addressing barriers. Full article
(This article belongs to the Special Issue HPV-Vaccines)
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Article
Compliance Indicators of COVID-19 Prevention and Vaccines Hesitancy in Kenya: A Random-Effects Endogenous Probit Model
Vaccines 2021, 9(11), 1359; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111359 - 19 Nov 2021
Viewed by 659
Abstract
Vaccine hesitancy remains a major public health concern in the effort towards addressing the COVID-19 pandemic. This study analyzed the effects of indicators of compliance with preventive practices on the willingness to take COVID-19 vaccines in Kenya. The data were from the COVID-19 [...] Read more.
Vaccine hesitancy remains a major public health concern in the effort towards addressing the COVID-19 pandemic. This study analyzed the effects of indicators of compliance with preventive practices on the willingness to take COVID-19 vaccines in Kenya. The data were from the COVID-19 Rapid Response Phone Surveys conducted between January and June 2021 during the fourth and fifth waves. The data were analyzed with the random-effects endogenous Probit regression model, with estimated parameters tested for robustness and stability. The results showed that willingness to take vaccines increased between the fourth and fifth waves. Compliance with many of the preventive practices also improved, although the utilizations of immune system-promoting practices were very low. The panel Probit regression results showed that compliance indicators were truly endogenous and there was existence of random effects. Immune system-boosting and contact-prevention indicators significantly increased and decreased the willingness to take vaccines, respectively (p < 0.01). The experience of mental health disorders in the form of nervousness and hopelessness also significantly influenced vaccine hesitancy (p < 0.10). Willingness to take vaccines also significantly increased among older people and those with a formal education (p < 0.01). Different forms of association exist between vaccine hesitancy and the prevention compliance indicators. There is a need to properly sensitize the people to the need to complement compliance with COVID-19 contact-prevention indicators with vaccination. Addressing mental health disorders in the form of loneliness, nervousness, depression, hopelessness and anxiety should also become the focus of public health, while efforts to reduce vaccine hesitancy should focus on individuals without formal education, males and youths. Full article
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Article
COVID-19 Vaccine Hesitancy and Attitude toward Booster Doses among US Healthcare Workers
Vaccines 2021, 9(11), 1358; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111358 - 19 Nov 2021
Cited by 2 | Viewed by 1206
Abstract
Vaccine reluctance among healthcare workers (HCW) can have widespread negative ramifications, including modeling behavior for the general population and challenges with maintaining a healthy workforce so we can respond to a resurgence of the pandemic. We previously reported that only one-third of HCW [...] Read more.
Vaccine reluctance among healthcare workers (HCW) can have widespread negative ramifications, including modeling behavior for the general population and challenges with maintaining a healthy workforce so we can respond to a resurgence of the pandemic. We previously reported that only one-third of HCW were willing to take the vaccine as soon as it became available prior to its Emergency Use Authorization (EUA). Here, we re-examine the attitude toward COVID-19 vaccines among HCW several months after the vaccines have been made widely available. In this study, only 7.9% (n = 107) of respondents were hesitant to take the first or second dose of the vaccine. Younger age (18–40 years) and lower level of education attainment (GED or less) were associated with higher vaccine hesitancy, whereas self-identified Asian racial identity was associated with greater acceptance of COVID-19 vaccination. Among the vaccine-hesitant group, more respondents noted mistrust of regulatory authorities (45.3%), government (48.6%), and pharmaceutical companies (50%) than mistrust of doctors (25.4%). Nearly two-thirds of respondents were concerned that vaccination may be ineffective against new strains and booster doses may be required; however, vaccine-hesitant respondents’ acceptance of a hypothetical booster dose was only 14.3%. Overall, vaccine hesitancy was observed to have demographic predictors similar to those previously reported; the hesitancy of some US HCW to receive booster doses may reflect a general hesitancy to receive other forms of vaccination. Full article
(This article belongs to the Special Issue New Insight in Vaccination and Public Health)
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Article
Antibody Titer Kinetics and SARS-CoV-2 Infections Six Months after Administration with the BNT162b2 Vaccine
Vaccines 2021, 9(11), 1357; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111357 - 19 Nov 2021
Viewed by 652
Abstract
Background: Studies reporting the long-term humoral response after receiving the BNT162b2 COVID-19 vaccine are important to drive future vaccination strategies. Yet, available literature is scarce. Covidiagnostix is a multicenter study designed to assess the antibody response in >1000 healthcare professionals (HCPs) who received [...] Read more.
Background: Studies reporting the long-term humoral response after receiving the BNT162b2 COVID-19 vaccine are important to drive future vaccination strategies. Yet, available literature is scarce. Covidiagnostix is a multicenter study designed to assess the antibody response in >1000 healthcare professionals (HCPs) who received the BNT162b2 vaccine. Methods: Serum was tested at time-0 (T0), before the first dose, T1, T2, and T3, respectively, 21, 42, and 180 days after T0. Antibodies against the SARS-CoV-2 nucleocapsid-protein were measured to assess SARS-CoV-2 infections, whereas antibodies against the receptor-binding domain of the spike protein were measured to assess the vaccine response. Neutralization activity against the D614G, B.1.1.7, and B.1.351 variants were also analyzed. Results: Six months post-vaccination HCPs showed an antibody titer decrease of approximately 70%, yet, the titer was still one order of magnitude higher than that of seropositive individuals before vaccination. We identified 12 post-vaccination infected HCPs. None showed severe symptoms. Interestingly, most of them showed titers at T2 above the neutralization thresholds obtained from the neutralization activity experiments. Conclusion: Vaccination induces a humoral response which is well detectable even six months post-vaccination. Vaccination prevents severe COVID-19 cases, yet post-vaccination infection is possible even in the presence of a high anti-S serum antibody titer. Full article
(This article belongs to the Special Issue Vaccination Coverage, Efficacy and Attitude in Targeted Risk Groups)
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Article
Commensal Bifidobacterium Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
Vaccines 2021, 9(11), 1356; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111356 - 18 Nov 2021
Viewed by 424
Abstract
A large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut [...] Read more.
A large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut microbiome can influence the antitumor activity of neo-epitope-based cancer vaccines in a BALB/c-CT26 cancer mouse model. Similarly to that observed in the C57BL/6-B16 model, Bifidobacterium administration per se has a beneficial effect on CT26 tumor inhibition. Furthermore, the combination of Bifidobacterium administration and vaccination resulted in a protection which was superior to vaccination alone and to Bifidobacterium administration alone, and correlated with an increase in the frequency of vaccine-specific T cells. The gut microbiome analysis by 16S rRNA gene sequencing and shotgun metagenomics showed that tumor challenge rapidly altered the microbiome population, with Muribaculaceae being enriched and Lachnospiraceae being reduced. Over time, the population of Muribaculaceae progressively reduced while the Lachnospiraceae population increased—a trend that appeared to be retarded by the oral administration of Bifidobacterium. Interestingly, in some Bacteroidales, Prevotella and Muribaculacee species we identified sequences highly homologous to immunogenic neo-epitopes of CT26 cells, supporting the possible role of “molecular mimicry” in anticancer immunity. Our data strengthen the importance of the microbiome in cancer immunity and suggests a microbiome-based strategy to potentiate neo-epitope-based cancer vaccines. Full article
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Review
A Review of the Implementation Status of and National Plans on HPV Vaccination in 17 Middle-Income Countries of the WHO Western Pacific Region
Vaccines 2021, 9(11), 1355; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111355 - 18 Nov 2021
Viewed by 616
Abstract
The World Health Organization’s Western Pacific Region is responsible for one-fourth of the global cervical cancer burden, and nearly 90% of that burden is concentrated in middle-income countries (MICs). Applying a conceptual model of implementation of population-based interventions, we synthesized the current implementation [...] Read more.
The World Health Organization’s Western Pacific Region is responsible for one-fourth of the global cervical cancer burden, and nearly 90% of that burden is concentrated in middle-income countries (MICs). Applying a conceptual model of implementation of population-based interventions, we synthesized the current implementation status of human papillomavirus (HPV) vaccination and national plans that form the basis of its implementation in 17 MICs. We gathered information from a range of governmental documents, published studies, and global databases. For all available national cancer-related plans and immunization plans, we examined the description of HPV vaccination. We found that, as of July 2021, only four countries (24%) had a mature HPV vaccination program with a high first-dose coverage; three (18%) had introduced HPV vaccination, but needed further efforts to scale it up, seven (41%) had not been able to introduce it after conducting demonstration projects, and three (18%) did not have any experience in HPV vaccination. In the national plans, most of the countries recognized the importance of HPV vaccination, but only 10 (59%) provided an implementation strategy on how it would be introduced or scaled up. Countries with a mature program were more likely to have their implementation strategy detailed in their national cancer control plan. Successful implementation of HPV vaccination requires overcoming known challenges and having a clear national plan. Positioning HPV vaccination clearly in the overall national cancer control plan may be key to accelerating its nationwide implementation. Full article
(This article belongs to the Special Issue Latest National HPV Vaccine Programs and Outcomes in the World)
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Article
Changing Features of COVID-19: Characteristics of Infections with the SARS-CoV-2 Delta (B.1.617.2) and Alpha (B.1.1.7) Variants in Southern Italy
Vaccines 2021, 9(11), 1354; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111354 - 18 Nov 2021
Viewed by 592
Abstract
Differences in the demographic and clinical characteristics of patients infected with the Alpha and Delta SARS-CoV-2 variants of concern in a large region of Southern Italy were assessed. Two cohorts of positive patients were compared. The Alpha group consisted of 11,135 subjects diagnosed [...] Read more.
Differences in the demographic and clinical characteristics of patients infected with the Alpha and Delta SARS-CoV-2 variants of concern in a large region of Southern Italy were assessed. Two cohorts of positive patients were compared. The Alpha group consisted of 11,135 subjects diagnosed between 21 March and 21 April 2021, and the Delta group consisted of 499 positive subjects diagnosed between 21 July and 21 August 2021. A descriptive and statistical analysis of the demographic and clinical characteristics of the two groups was performed. The proportion of patients with mild and moderate infections was significantly higher in the Delta than in the Alpha group (p < 0.001). In fully vaccinated patients, the proportion of symptomatic individuals was significantly higher in the Delta than in the Alpha group. The Delta group showed odds ratios of 3.08 (95% CI, 2.55–3.72) for symptomatic infection and 2.66 (95% CI, 1.76–3.94) for hospitalization. Improving COVID-19 vaccination rates is a priority, since infection with the SARS-CoV-2 Delta variant has a significant impact on patient outcomes. Additional targeted prevention strategies such as social distancing, the use of masks in indoor settings irrespective of vaccination status, and the use of a sanitary passport could be crucial to contain further spread of SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Epidemiology of COVID-19)
Case Report
Autoantibody Release in Children after Corona Virus mRNA Vaccination: A Risk Factor of Multisystem Inflammatory Syndrome?
Vaccines 2021, 9(11), 1353; https://doi.org/10.3390/vaccines9111353 - 18 Nov 2021
Cited by 3 | Viewed by 9556
Abstract
Multisystem inflammatory syndrome (MIS) is a new systemic inflammatory acute onset disease that mainly affects children (MIS-C) and, at a lesser frequency, adults (MIS-A); it typically occurs 3–6 weeks after acute SARS-CoV infection. It has been postulated and shown in adults that MIS [...] Read more.
Multisystem inflammatory syndrome (MIS) is a new systemic inflammatory acute onset disease that mainly affects children (MIS-C) and, at a lesser frequency, adults (MIS-A); it typically occurs 3–6 weeks after acute SARS-CoV infection. It has been postulated and shown in adults that MIS may occur after SARS-CoV-2 vaccination (MIS-V). Our current case is one of the first published cases with a multisystem inflammatory syndrome in an 18-year-old adolescent after the SARS-CoV-2 vaccine from Pfizer/BionTech (BNT162b2), who fulfills the published level 1 criteria for a definitive disease: age < 21 years, fever > 3 consecutive days, pericardial effusion, elevated CRP/NT-BNP/Troponin T/D-dimeres, cardiac involvement, and positive SARS-CoV-2 antibodies. The disease starts 10 weeks after the second vaccination, with a fever (up to 40 °C) and was treated with amoxicillin for suspected pneumonia. The SARS CoV-2-PCR and several antigen tests were negative. With an ongoing fever, he was hospitalized 14 days later. A pericardial effusion (10 mm) was diagnosed by echocardiography. The C-reactive protein (174 mg/L), NT-BNP (280 pg/mL), and Troponin T (28 pg/mL) values were elevated. Due to highly elevated D-dimeres (>35,000 μg/L), a pulmonary embolism was excluded by thoracal computer tomography. If the boy did not improve with intravenous antibiotics, he was treated with intravenous immunoglobulins; however, the therapy was discontinued after 230 mg/kg if he developed high fever and hypotension. A further specialized clinic treated him with colchicine and ibuprofen. The MIS-V was discovered late, 4 months after the onset of the disease. As recently shown in four children with MIS-C after SARS-CoV-2 infection and a girl with Hashimoto thyroiditis after BNT162b2 vaccination, we found elevated functional autoantibodies against G-protein-coupled receptors that may be important for pathophysiology but are not conclusive for the diagnosis of MIS-C. Conclusion: We are aware that a misattribution of MIS-V as a severe complication of coronavirus vaccination can lead to increased vaccine hesitancy and blunt the global COVID-19 vaccination drive. However, the pediatric population is at a higher risk for MIS-C and a very low risk for COVID-19 mortality. The publication of such cases is very important to make doctors aware of this complication of the vaccination, so that therapy with intravenous immunoglobulins can be initiated at an early stage. Full article
(This article belongs to the Special Issue Assessment of Post-COVID-19 Complications and Vaccination Efficacy)
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Article
Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
Vaccines 2021, 9(11), 1352; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111352 - 18 Nov 2021
Viewed by 426
Abstract
To mount an adequate immune response against pathogens, stepwise mutation and selection processes are crucial functions of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of [...] Read more.
To mount an adequate immune response against pathogens, stepwise mutation and selection processes are crucial functions of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of the single-cell transcriptome as well as the B-cell receptor (BCR) repertoire (scBCR-rep) in plasma cells of an immunized donor and compared it with baseline B-cell characteristics as well as flow cytometry findings. Based on the flow cytometry knowledge and literature findings, we discriminated individual B-cell subsets in the transcriptomics data and traced over-time maturation of plasmablasts/plasma cells (PB/PCs) and identified the pathways associated with the plasma cell maturation. We observed that the repertoire in PB/PCs differed from the baseline B-cell repertoire e.g., regarding expansion of unique clones in post-vaccination visits, high usage of IGHG1 in expanded clones, increased class-switching events post-vaccination represented by clonotypes spanning multiple IGHC classes and positive selection of CDR3 sequences over time. Importantly, the Variable gene family-based clustering of BCRs represented a similar measure as the gene-based clustering, but certainly improved the clustering of BCRs, as BCRs from duplicated Variable gene families could be clustered together. Finally, we developed a query tool to dissect the immune response to the components of the Boostrix vaccine. Using this tool, we could identify the BCRs related to anti-tetanus and anti-pertussis toxoid BCRs. Collectively, we developed a bioinformatic workflow which allows description of the key features of an ongoing (longitudinal) immune response, such as activation of PB/PCs, Ig class switching, somatic hypermutation, and clonal expansion, all of which are hallmarks of antigen exposure, followed by mutation & selection processes. Full article
(This article belongs to the Special Issue Bordetella pertussis Infection and Vaccination)
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Review
Maternal COVID-19 Vaccination and Its Potential Impact on Fetal and Neonatal Development
Vaccines 2021, 9(11), 1351; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111351 - 18 Nov 2021
Viewed by 4459
Abstract
Vaccines have been developed at “warp speed” to combat the COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Although they are considered the best approach for preventing mortality, when assessing the safety of these vaccines, pregnant women have not been included in clinical trials. [...] Read more.
Vaccines have been developed at “warp speed” to combat the COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Although they are considered the best approach for preventing mortality, when assessing the safety of these vaccines, pregnant women have not been included in clinical trials. Thus, vaccine safety for this demographic, as well as for the developing fetus and neonate, remains to be determined. A global effort has been underway to encourage pregnant women to get vaccinated despite the uncertain risk posed to them and their offspring. Given this, post-hoc data collection, potentially for years, will be required to determine the outcomes of COVID-19 and vaccination on the next generation. Most COVID-19 vaccine reactions include injection site erythema, pain, swelling, fatigue, headache, fever and lymphadenopathy, which may be sufficient to affect fetal/neonatal development. In this review, we have explored components of the first-generation viral vector and mRNA COVID-19 vaccines that are believed to contribute to adverse reactions and which may negatively impact fetal and neonatal development. We have followed this with a discussion of the potential for using an ovine model to explore the long-term outcomes of COVID-19 vaccination during the prenatal and neonatal periods. Full article
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Article
ISCOM-like Nanoparticles Formulated with Quillaja brasiliensis Saponins Are Promising Adjuvants for Seasonal Influenza Vaccines
Vaccines 2021, 9(11), 1350; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111350 - 18 Nov 2021
Viewed by 441
Abstract
Vaccination is the most effective public health intervention to prevent influenza infections, which are responsible for an important burden of respiratory illnesses and deaths each year. Currently, licensed influenza vaccines are mostly split inactivated, although in order to achieve higher efficacy rates, some [...] Read more.
Vaccination is the most effective public health intervention to prevent influenza infections, which are responsible for an important burden of respiratory illnesses and deaths each year. Currently, licensed influenza vaccines are mostly split inactivated, although in order to achieve higher efficacy rates, some influenza vaccines contain adjuvants. Although split-inactivated vaccines induce mostly humoral responses, tailoring mucosal and cellular immune responses is crucial for preventing influenza infections. Quillaja brasiliensis saponin-based adjuvants, including ISCOM-like nanoparticles formulated with the QB-90 saponin fraction (IQB90), have been studied in preclinical models for more than a decade and have been demonstrated to induce strong humoral and cellular immune responses towards several viral antigens. Herein, we demonstrate that a split-inactivated IQB90 adjuvanted influenza vaccine triggered a protective immune response, stronger than that induced by a commercial unadjuvanted vaccine, when applied either by the subcutaneous or the intranasal route. Moreover, we reveal that this novel adjuvant confers up to a ten-fold dose-sparing effect, which could be crucial for pandemic preparedness. Last but not least, we assessed the role of caspase-1/11 in the generation of the immune response triggered by the IQB90 adjuvanted influenza vaccine in a mouse model and found that the cellular-mediated immune response triggered by the IQB90-Flu relies, at least in part, on a mechanism involving the casp-1/11 pathway but not the humoral response elicited by this formulation. Full article
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Case Report
Retinal Vascular Events after mRNA and Adenoviral-Vectored COVID-19 Vaccines—A Case Series
Vaccines 2021, 9(11), 1349; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111349 - 17 Nov 2021
Cited by 3 | Viewed by 821
Abstract
Background: To describe cases of retinal vascular events shortly after administration of mRNA or adenoviral-vectored COVID-19 vaccines. Design: Retrospective, multicenter case series. Methods: Six cases of retinal vascular events shortly after receiving COVID-19 vaccines. Results: A 38-year-old, otherwise healthy male patient presented with [...] Read more.
Background: To describe cases of retinal vascular events shortly after administration of mRNA or adenoviral-vectored COVID-19 vaccines. Design: Retrospective, multicenter case series. Methods: Six cases of retinal vascular events shortly after receiving COVID-19 vaccines. Results: A 38-year-old, otherwise healthy male patient presented with branch retinal arterial occlusion four days after receiving his second dose of SARS-CoV-2 vaccination with Comirnaty® (BioNTech®, Mainz, Germany; Pfizer®, New York City, NY, USA). An 81-year-old female patient developed visual symptoms twelve days after the second dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with a combined arterial and venous occlusion in her right eye. A 40-year-old male patient noticed blurry vision five days after his first dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with venous stasis retinopathy in his left eye. A 67-year-old male was diagnosed with non-arteritic anterior ischemic optic neuropathy in his right eye four days after receiving the first dose of Vaxzevria® (AstraZeneca®, Cambridge, UK). A 32-year-old man presented with a sudden onset of a scotoma two days after receiving the second dose of SARS-CoV-2 vaccination with Spikevax® (Moderna, Cambridge, UK) and was diagnosed with a circumscribed nerve fiber infarction. A 21-year-old female patient developed an acute bilateral acute macular neuroretinopathy three days after receiving the first dose of SARS-CoV2-vaccine Vaxzevria® (AstraZeneca®, Cambridge, UK). Conclusion: This case series describes six cases of retinal vascular events shortly after receiving mRNA or adenoviral-vectored COVID-19 vaccines. The short time span between received vaccination and occurrence of the observed retinal vascular events raises the question of a direct correlation. Our case series adds to further reports of possible side effects with potential serious post-immunization complications of COVID-19 vaccinations. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Article
Vaccine Knowledge, Awareness and Hesitancy: A Cross Sectional Survey among Parents Residing at Sandakan District, Sabah
Vaccines 2021, 9(11), 1348; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111348 - 17 Nov 2021
Viewed by 790
Abstract
Background: Incomplete childhood immunization against communicable diseases is a major concern and vaccine hesitancy remains a hurdle to overcome in primary vaccination programs. This study was to examine the parents’ vaccine knowledge, awareness and hesitancy in relation to their children’s immunization status. Methods: [...] Read more.
Background: Incomplete childhood immunization against communicable diseases is a major concern and vaccine hesitancy remains a hurdle to overcome in primary vaccination programs. This study was to examine the parents’ vaccine knowledge, awareness and hesitancy in relation to their children’s immunization status. Methods: A cross-sectional questionnaire study design was used. The parents who brought their children for immunization visit or follow-up at four public health clinics located in Sandakan district were invited to participate in this survey. Informed consent was obtained before each participant completed a hard copy of self-administered questionnaire in either English or Malay versions. Results: Of 405 parents responded, they generally had good knowledge and awareness of vaccines, only a small percentage (6.8%) of parents were found vaccine hesitant. There were significant differences in vaccine knowledge and awareness in those from different education levels and employment status; similarly, these two factors also significantly affected the vaccine hesitancy among the parents. The parents’ knowledge score was found to be moderately associated with their awareness (r = 0.551, p < 0.01) and inversely correlated to vaccine hesitancy (r = −0.397, p < 0.01). Most of the children (n = 376, 92.8%) in the study were immunized. The children’s immunization status was significantly associated with the parents’ education level (p = 0.025). There was also a significant difference in the total vaccine knowledge scores between the groups of parents with different child immunization status (p = 0.05). Conclusion: This study revealed that parents with higher education had a better knowledge of vaccinations, were less vaccine hesitant and were more likely to ensure that their children complete the recommended course of immunization. It is crucial to ensure parents are well-informed about the safety and efficacy of vaccines so that the children are protected from communicable diseases by the child vaccination program. Full article
(This article belongs to the Special Issue Factors Associated with Vaccine Hesitancy)
Article
Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
Vaccines 2021, 9(11), 1347; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111347 - 17 Nov 2021
Cited by 1 | Viewed by 757
Abstract
Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain [...] Read more.
Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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Article
CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology
Vaccines 2021, 9(11), 1346; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111346 - 17 Nov 2021
Viewed by 526
Abstract
We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable [...] Read more.
We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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Review
The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview
Vaccines 2021, 9(11), 1345; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111345 - 17 Nov 2021
Cited by 1 | Viewed by 783
Abstract
In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has [...] Read more.
In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has several advantages to vaccine development compared to other platforms, such as lower coast, the absence of cell cultures, and the possibility to combine different targets. During the COVID-19 pandemic, the use of mRNA as a vaccine became more relevant; two out of the four most widely applied vaccines against COVID-19 in the world are based on this platform. However, even though it presents advantages for vaccine application, mRNA technology faces several pivotal challenges to improve mRNA stability, delivery, and the potential to generate the related protein needed to induce a humoral- and T-cell-mediated immune response. The application of mRNA to vaccine development emerged as a powerful tool to fight against cancer and non-infectious and infectious diseases, for example, and represents a relevant research field for future decades. Based on these advantages, this review emphasizes mRNA and self-amplifying RNA (saRNA) for vaccine development, mainly to fight against COVID-19, together with the challenges related to this approach. Full article
(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)
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Case Report
Complicated Long Term Vaccine Induced Thrombotic Immune Thrombocytopenia—A Case Report
Vaccines 2021, 9(11), 1344; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111344 - 17 Nov 2021
Cited by 2 | Viewed by 1330
Abstract
Background and Objectives: Vaccine induced thrombotic thrombocytopenia (VITT) may occur after COVID-19 vaccination with recombinant adenoviral vector-based vaccines. VITT can present as cerebral sinus and venous thrombosis (CSVT), often complicated by intracranial hemorrhage. Today it is unclear, how long symptomatic VITT can persist. [...] Read more.
Background and Objectives: Vaccine induced thrombotic thrombocytopenia (VITT) may occur after COVID-19 vaccination with recombinant adenoviral vector-based vaccines. VITT can present as cerebral sinus and venous thrombosis (CSVT), often complicated by intracranial hemorrhage. Today it is unclear, how long symptomatic VITT can persist. Here, we report the complicated long-term course of a VITT patient with extremely high titers of pathogenic anti-platelet factor 4 (PF4)-IgG antibodies. Methods: Clinical and laboratory findings are presented, including the course of platelet counts, D-Dimer levels, clinical presentation, imaging, SARS-CoV-2-serological and immunological, platelet activating anti-PF4-IgG, as well as autopsy findings. Results: The patient presented with extended superior sagittal sinus thrombosis with accompanying bifrontal intracerebral hemorrhage. Repeated treatment with intravenous immune globuline (IVIG) resolved recurrent episodes of thrombocytopenia. Moreover, the patient’s serum remained strongly positive for platelet-activating anti-PF4-IgG over three months. After a period of clinical stabilization, the patient suffered a recurrent and fatal intracranial hemorrhage. Conclusions: Complicated VITT with extremely high anti-PF4-IgG titers over three months can induce recurrent thrombocytopenia despite treatment with IVIG and anticoagulation. Plasma exchange, immunoadsorption, and /or immunosuppressive treatment may be considered in complicated VITT to reduce extraordinarily high levels of anti-PF4-IgG. Long-term therapy in such cases must take the individual bleeding risk and CSVT risk into account. Full article
(This article belongs to the Section Innate and Adaptive Immunity in Vaccination)
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