Vaccines, Volume 9, Issue 7 (July 2021) – 122 articles

The World Health Organization (WHO) has placed N. gonorrhoeae on the global priority list of antimicrobial resistant pathogens and is urgently seeking the development of new intervention strategies. N. gonorrhoeae causes 86.9 million cases globally per annum. The effects of gonococcal disease are seen predominantly in women and children and especially in the Australian Indigenous community. While economic modelling suggests that this infection alone may directly cost the USA health care system USD 11.0–20.6 billion, indirect costs associated with adverse disease and pregnancy outcomes, disease prevention, and productivity loss, mean that the overall effect of the disease is far greater still. In this review, we summate the current progress towards the development of a gonorrhea vaccine and describe the clinical trials being undertaken in Australia to assess the efficacy of the current formulation of Bexsero^® in controlling disease. Full article

Despite numerous efforts to develop an effective vaccine against Pseudomonas aeruginosa, no vaccine has yet been approved for human use. This study investigates the utility of the P. aeruginosa inherently produced polyhydroxyalkanaote (PHA) inclusions and associated host–cell proteins (HCP) as a particulate vaccine platform. We further engineered PHA inclusions to display epitopes derived from the outer membrane proteins OprF/OprI/AlgE (Ag) or the type III secretion system translocator PopB. PHA and engineered PHA beads induced antigen-specific humoral, cell-mediated immune responses, anti-HCP and anti-polysaccharide Psl responses in mice. Antibodies mediated opsonophagocytic killing and serotype-independent protective immunity as shown by 100% survival upon challenge with P. aeruginosa in an acute pneumonia murine model. Vaccines were stable at 4 °C for at least one year. Overall, our data suggest that vaccination with subcellular empty PHA beads was sufficient to elicit multiple immune effectors that can prevent P. aeruginosa infection. Full article

Background: Racial/ethnic minorities generally have a lower knowledge of human papillomavirus (HPV) and the HPV vaccine than non-Hispanic Whites. They are also less likely to have a regular healthcare provider (HCP). Given the role of HCPs in disseminating health information, we evaluated whether racial/ethnic disparities in HPV knowledge are moderated by regular HCP status. Methods: Data from the Health Information National Trends Survey Five (HINTS 5) Cycles One and Two (2017–2018) were analyzed. HPV and HPV vaccine knowledge were compared by regular HCP status across race/ethnicities. Independent partially-adjusted multivariable logistic regression models were used to assess the association between race/ethnicity and knowledge after controlling for sociodemographic characteristics. The resulting adjusted odds ratios were compared to those from fully-adjusted models that included HCP status. Results: After adjusting for regular HCP status, differences in knowledge persisted between racial/ethnic groups. Compared to Whites, Hispanics and Other race/ethnicities had significantly lower odds of having heard of HPV. Blacks, Hispanics, and Other race/ethnicities had significantly lower odds of having heard of the HPV vaccine. Conclusion: Racial/ethnic minorities had significantly lower levels of knowledge despite HCP status. These data suggest the need to address disparities in health information and strengthen provider–patient communication regarding HPV and the HPV vaccine. Full article

Italy was one of the first industrialized countries to implement a program of routine vaccination against hepatitis B virus (HBV) infection. However, currently, no HBV vaccine is administered at birth if the screened mother is HBsAg negative, whilst babies born to HBsAg positive mothers are given vaccine and hepatitis B immunoglobulin, within 12–24 post-delivery hours. A single center retrospective analysis of policies and practices to prevent mother-to-child transmission of HBV was carried out, to evaluate their adherence to HBV care guidelines. Paired maternal-infant medical records for consecutive live births, between January 2015 and December 2019, were reviewed at the AOU Città della Salute e Scienza di Torino, where a total of 235/35,506 babies (0.7%) were born to HBsAg positive mothers. Markers of active viral replication, i.e., HBV DNA level and/or HBeAg, were reported in only 66/235 (28%) of the mothers’ medical records. All newborns had immunoprophylaxis at birth: 61% at <12 h, 31% between 12 and 24 h, 7% between 24 and 36 h and 1% at >36 h. In 2019, two cases of vertical HBV transmission occurred, despite timely immunoprophylaxis, as their mothers’ viral load was detected too late for antiviral prophylaxis. Missed early identification of pregnant women with high viremia levels or late vaccinations may contribute to perinatal HBV infection. Immunoprophylaxis should be given to babies born to HBsAg positive mothers at the latest within 12 h. In Italy, policies aimed at achieving the WHO 2030 goal of eliminating viral hepatitis should be further implemented. Full article

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children, and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of an HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation to stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations, along with attenuating mutations E580G and S660A, in PB1 of B/Bris (B/Bris PB1att 4M). Serial passages of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine. Full article

Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples; gene expression was determined by microarray method. In gene set enrichment analysis, responders showed an up-regulation of 14 gene sets (TNF-alpha/NFkB pathway, inflammatory response, the complement system, Il6 and Il2 JAK-STAT signaling, among others) and a down-regulation of 7 gene sets (such as E2F targets or interferon alpha response). The expression of genes regulated by three (miR-223-3p, miR-1183 and miR-8063) of the 9 differentially expressed miRNAs was significantly down-regulated in responders. The deregulation of certain gene sets related to inflammatory processes seems fundamental for viral control, and certain miRNAs may be important in fine-tuning these processes. Full article

Vaccine uptake could influence vaccination efforts to control the widespread COVID-19 pandemic; however, little is known about vaccine acceptance in Saudi Arabia. The present study aimed to assess the Saudi public’s intent to get vaccinated against COVID-19 and explore the associated demographic determinants of their intentions as well as the reasons for vaccine hesitancy. A cross-sectional, web-based survey was distributed to public individuals in Saudi Arabia between 25 December 2020 and 15 February 2021. Participants were asked if they were willing to get vaccinated, and the responses, along with demographic data were entered into a multinomial logistic regression model to assess the relative risk ratio (RRR) for responding “no” or “unsure” versus “yes”. Among 3048 participants (60.1% female, 89.5% Saudi), 52.9% intend to get vaccinated, 26.8% were unsure, and 20.3% refused vaccination. Vaccine hesitancy was significantly higher among females (RRR = 2.70, p < 0.0001) and those who had not been recently vaccinated for influenza (RRR = 2.63, p < 0.0001). The likelihood was lower among Saudis (RRR = 0.49, p < 0.0001), those with less than a secondary education (RRR = 0.16, p < 0.0001), perceived risks of COVID-19, and residents of the southern region (RRR = 0.46, p < 0.0001). The most often cited reasons for hesitancy were short clinical testing periods and concerns about adverse events or effectiveness. Vaccine hesitancy is mediated by many demographic factors and personal beliefs. To address vaccine-related concerns and amend deeply rooted health beliefs, communication should provide transparent information. Full article

Coronavirus disease (COVID-19) pandemic caused by the coronavirus SARS-CoV-2 represents an enormous challenge to global public health, with thousands of infections and deaths in over 200 countries worldwide. The purpose of this study was to identify SARS-CoV-2 epitopes with potential to interact in silico with the alleles of the human leukocyte antigen class I (HLA I) and class II (HLA II) commonly found in the Colombian population to promote both CD4 and CD8 immune responses against this virus. The generation and evaluation of the peptides in terms of HLA I and HLA II binding, immune response, toxicity and allergenicity were performed by using computer-aided tools, such as NetMHCpan 4.1, NetMHCIIpan 4.0, VaxiJem, ToxinPred and AllerTop. Furthermore, the interaction between the predicted epitopes with HLA I and HLA II proteins frequently found in the Colombian population was studied through molecular docking simulations in AutoDock Vina and interaction analysis in LigPlot+. One of the promising peptides proposed in this study is the HLA I epitope YQPYRVVVL, which displayed an estimated coverage of over 82% and 96% for the Colombian and worldwide population, respectively. These findings could be useful for the design of new epitope-vaccines that include Colombia among their population target. Full article

Introduction: Despite the widespread availability of vaccines, the incidence of vaccine-preventable childhood diseases (VPCD) started to grow in recent years. The aim of the study was to compare the annual incidence of selected VPCDs in the EU (European Union) and EFTA (European Free Trade Association) countries in the period of the last 5 years (2014–2019 or other intervals, depending on data availability), and the country-specific vaccine schedules. Methods: VPCD incidence rates in Europe were based on “The Surveillance Atlas of Infectious Diseases” by the ECDC (European Centre for Disease Prevention and Control); vaccination schedules were based on ECDC reports. Results: The obligation to vaccinate was not universal, and it generally only applied to two preparations: the MMR (measles, mumps, rubella) vaccine and the one against polio. During the study, the situation associated with mumps did not change or improve in individual countries; the median incidence amounted to 30 cases. The median incidence associated with rubella amounted to 1 case, but in a few countries, it grew very rapidly, i.e., in Germany, Italy, and Romania; in Poland, the incidence was clearly decreasing, from 5923 to 1532 cases. The most dynamic situation concerned measles. The total median was 2.4 cases per 100,000 population; the only one country with falling incidence was Germany. The diseases associated with Streptococcus pneumoniae and Neisseria meningitidis remained at a stable level in all analyzed countries. Conclusion: Vaccine schedules differ among the countries, so does the epidemiological situation of selected diseases. Morbidity on measles was the most disturbing phenomenon: the incidence rate increased in almost 40% of all countries, regardless of the obligation to vaccinate. The increasing incidence of VPCD may be due to anti-vaccine movements, the activity of which is often caused by mistrust and spreading misinformation. In order to better prevent the increase in morbidity, standardization of vaccine schedules and documentation should be considered in the EU countries. Full article

One important strategy to increase vaccination coverage is to minimize missed opportunities for vaccination. Missed opportunities for simultaneous vaccination (MOSV) occur when a child receives one or more vaccines but not all those for which they are eligible at a given visit. Household surveys that record children’s vaccination dates can be used to quantify occurrence of MOSVs and their impact on achievable vaccination coverage. We recently automated some MOSV analyses in the World Health Organization’s freely available software: Vaccination Coverage Quality Indicators (VCQI) making it straightforward to study MOSVs for any Demographic & Health Survey (DHS), Multi-Indicator Cluster Survey (MICS), or Expanded Programme on Immunization (EPI) survey. This paper uses VCQI to analyze MOSVs for basic vaccine doses among children aged 12–23 months in four rounds of DHS in Colombia (1995, 2000, 2005, and 2010) and five rounds of DHS in Nigeria (1999, 2003, 2008, 2013, and 2018). Outcomes include percent of vaccination visits MOSVs occurred, percent of children who experienced MOSVs, percent of MOSVs that remained uncorrected (that is, the missed vaccine had still not been received at the time of the survey), and the distribution of time-to-correction for children who received the MOSV dose at a later visit. Full article

The COVID-19 pandemic, a source of fear and anxiety worldwide, has caused many adverse impacts. Collaborative efforts to end COVID-19 have included extensive research on vaccines. Many vaccination campaigns have been launched in many countries, including Vietnam, to create community immunization. However, citizens’ willingness to participate is a prerequisite for effective vaccination programs and other related policies. Among all demographic groups, participation rates among young adults are of interest because they are an important workforce and are a source of high infection risk in the community. In March 2021, a pool of approximately 6000 participants in Ho Chi Minh City were randomly polled using an email-based online survey. The exploratory results of 398 valid observations show that students’ perceptions of the dangers of COVID-19 and the importance of vaccination were both relatively high (4.62/5 and 4.74/5, respectively). Furthermore, 83.41 percent of students polled (n = 332) chose vaccination, while 16.59 percent chose hesitation (n = 64) and not to be vaccinated (n = 2). More importantly, our estimated results of the Bayesian regression model (BRM) show that the perceived importance of the vaccine, concerns about the vaccine’s side effects, and a lack of access to information are the top three reasons for their reluctance and/or refusal to get vaccinated. These findings are a valuable resource for politicians, researchers, and those interested in COVID-19 vaccinations to devise and execute campaigns to effectively combat this terrifying pandemic. Full article

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection. Full article

Emerging efficacy and safety data have led to the authorization of COVID-19 vaccines worldwide, but most trials excluded patients with active malignancies. This study evaluates the intended acceptance of COVID-19 vaccination in cancer patients in Hong Kong. Methods: 660 adult cancer patients received a survey, in paper or electronic format, between 31 January 2021 and 15 February 2021. The survey included patient’s clinical characteristics, perceptions of COVID-19 and vaccination, vaccine knowledge, cancer health literacy, and Hospital Anxiety and Depression scale (HADS). The primary outcome was the intended acceptance of COVID-19 vaccine in cancer patients. Multivariable analysis was performed to identify factors associated with intended acceptance. Results: The intended acceptance of COVID-19 vaccination was 17.9%. A total of 487 (73.8%) believed that vaccination could prevent them from infection. Over 70% worried about vaccine negative effects on cancer and its side effects. Factors associated with intended acceptance included higher level of “belief in vaccine on preventing them from getting COVID-19”, less worry about long-term side effects of vaccine, lower level of cancer health literacy, and normal HADS (Depression scale). Conclusions: To improve vaccine acceptance rate, public education campaigns specific to cancer patients to gain their trust in efficacy and relieve their worries are needed. Full article

The potential of Eimeria parasites as live vaccine vectors has been reported with successful genetic manipulation on several species like E. tenella, E. mitis and E. necatrix. Among seven Eimeria species infecting chickens, E. acervulina is a highly prevalent, moderately pathogenic species. Thus, it is valuable for the study of transfection and for use as a potential as vaccine vector. In this study, a plasmid containing expression cassette with enhanced yellow fluorescent protein (EYFP), red fluorescent protein (RFP) and 12 copies of extracellular domain of H9N2 avian influenza virus M2 (M2e) protein was used for the transfection. Nucleofected sporozoites were inoculated into birds through wing vein. Recombinant E. acervulina oocysts with 0.1% EYFP+ and RFP+ populations were collected from the feces of the inoculated birds. The fluorescent rate of transgenic parasites reached over 95% after nine successive propagations with a pyrimethamine selection in vivo and fluorescent-activated cell sorting (FACS) of progeny oocysts. The expression of M2e in the transgenic parasites (EaM2e) was confirmed by Western blot and its cytoplasm localization in sporozoites was displayed by an indirect immunofluorescent assay (IFA). Meanwhile, we found that the fecundity of EaM2e was equivalent to that of wild type E. acervulina (EaWT). Taken together, the stable transfection of E. acervulina was successfully established. Future studies will focus on whether transgenic E. acervulina can serve as a live vaccine vector. Full article

Acceptance of the COVID-19 vaccine will play a crucial role in combating the current pandemic. Vaccine rollouts have started in most countries. To reach the desirable vaccine coverage and to enhance its uptake, it is imperative to assess vaccine hesitancy. Methods: To assess the current vaccine acceptability in Austria and its influencing factors, an online survey was created and comprised fifteen questions segmented into a sociodemographic part and the acceptance and influencing factors of the approval of the COVID-19 vaccine. Results: In total, 70% of the 1350 respondents thought that the COVID-19 vaccine is an effective way to prevent and control the virus, while 13% disagreed and 17% were uncertain. Further, 71% approved the rapid development and rollout of the vaccine, while 55% were willing to accept the vaccine as soon as it became available, 18% did not want to get the vaccine, 17% wanted to delay, and 10% were already vaccinated. Conclusions: The results show a generally positive attitude towards the new COVID-19 vaccine. The doctor’s recommendation greatly influences the decision-making process, and tailored vaccine information can support a higher vaccine coverage. Full article

Background: A pneumococcal carriage surveillance study took place examining Jordanian children in urban and rural areas in the period 2015–2019. Objectives: To determine urban and rural differences in pneumococcal carriage rate, resistance, and serotypes among healthy Jordanian children from Amman (urban) and eastern Madaba (rural). Methods: Nasopharyngeal swabs (NP) were taken from 682 children aged 1 to 163 months. Pneumococcal identification, serotyping, and resistance were performed according to standard method. Results: The number of cases tested for Amman was 267 and there were 415 cases tested for eastern Madaba. Carriage rate for eastern Madaba was 39.5% and 31.1% for Amman. Predominant serotypes for eastern Madaba and Amman were 19F (21.3%; 15.7%), 23F (12.2%; 9.6%), 14 (6.7%; 2.4%), 19A (4.9%; 2.4%), and 6A (5.5%; 3.6%). Resistance rates for eastern Madaba and Amman were as follows: penicillin (95.8%; 81.9%), clarithromycin (68.9%; 59.0%), clindamycin (40.8%; 31.3%), and trimethoprim-sulfamethoxazole (73.2%; 61.4%). Coverage of PCV7, PCV13, and the future PCV20 for Amman was 42.2%, 48.2%, and 60.2%; for eastern Madaba, coverage was 50.0%, 62.2%, and 73.2%, respectively. In Amman 25.8% of children received 1–3 PCV7 injections compared to 1.9% of children in eastern Madaba. Conclusions: There were significant differences in carriage, resistance, and coverage between both regions. The potential inclusion of a PCV vaccination program for rural areas is essential. Full article

Vaccination programs are considered a central pillar of the efforts to stop COVID-19. However, vaccine doses are scarce and several organizational and logistical obstacles, such as the timing of and reserves for second shots and delivery failures, apparently slow down vaccination roll-outs in several countries. Moreover, it is an open question as to where vaccines are administered as efficiently as possible (vaccination centers, hospitals, doctor’s offices, pharmacists, etc.). The first aim of our study was to systematically evaluate the efficiency of a country’s vaccination campaign. The second aim was to analyze how the integration of doctors’ offices into a campaign that formerly relied only on vaccination centers affected the speed of that campaign. Using data on vaccine deliveries and vaccinations given in Germany, we find considerable differences across federal states in terms of efficiency, defined as the ability to administer the most vaccinations out of a given number of available doses. Back-of-the-envelope calculations for January to May 2021 show that vaccinations would have been 3.4–6.9% higher if all federal states had adopted a similar ratio between vaccinations given and vaccines stored, as the most efficient states did. This corresponds to 1.7–3.3% of Germany’s total population. In terms of our second research goal, we find evidence that the integration of doctors’ offices into the vaccination campaign significantly increased the ratio of vaccinations administered out of a given stock of vaccine doses. On average, there appears to be a structural break in this ratio after doctors’ offices were integrated into the vaccination campaign on 5 April 2021. On average, an additional 11.6 out of 100 available doses were administered each week compared to the period prior to that date. We conclude that there are considerable regional differences in the efficiency of the vaccination roll-out. Systematic efficiency analyses are one step to detecting inefficiencies and to identify best practices that can be adopted to eventually speed up the vaccination roll-out in a country. Full article

Animal models have been an important tool for the development of influenza virus vaccines since the 1940s. Over the past 80 years, influenza virus vaccines have evolved into more complex formulations, including trivalent and quadrivalent inactivated vaccines, live-attenuated vaccines, and subunit vaccines. However, annual effectiveness data shows that current vaccines have varying levels of protection that range between 40–60% and must be reformulated every few years to combat antigenic drift. To address these issues, novel influenza virus vaccines are currently in development. These vaccines rely heavily on animal models to determine efficacy and immunogenicity. In this review, we describe seasonal and novel influenza virus vaccines and highlight important animal models used to develop them. Full article

(1) Background: There are currently limited treatments for castration-resistant prostate cancer. Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management. BCG plays a vital role in treating bladder cancer, mainly by inducing immune activation, but is rarely used for prostate cancer. (2) Methods: The TCGA database, PCR, and Western blotting were used to analyze the expression of STEAP1 in mouse and human tissues. Then, we constructed a fusion protein vaccine with Mycobacterium tuberculosis Ag85B and three repeated octapeptide epitopes of a six-transmembrane epithelial antigen of the prostate 1 (STEAP1_186-193), Ag85B-3×STEAP1_186-193. The uptake of the fusion protein vaccine by DCs was evaluated by confocal microscopy, and DC markers were detected using flow cytometry after incubation with the fusion protein. The immune response against prostate cancer was evaluated by the LDH assay and xenografts in vitro and in vivo. Then, the tumor microenvironment was determined using IHC and ELISA. In addition, the epitope was mutated using CRISPR-Cas9 to illustrate that the fusion protein elicited immunization against STEAP1. (3) Results: The TCGA database analysis, PCR, and Western blotting showed that STEAP1 was highly expressed in human and murine prostate cancer. After the uptake of the purified fusion protein vaccine by DCs, CD11c, CD80, CD86, and MHC II were upregulated and triggered a cytotoxic T lymphocyte (CTL) response against TRAMP-C1 and RM1 cells in vitro. Furthermore, the fusion protein vaccine inhibited tumor growth and improved the tumor microenvironment in vivo, with more CD3⁺ cells and fewer FOXP3⁺ cells in the tumor. Serum IFN-γ and IL-2 were significantly higher than in the control group, while IL-4 expression was lower, indicating that the fusion protein vaccine activated Th1 immunity. The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) Conclusion: In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund’s adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer. Full article

Objective: The objective of this research is to demonstrate the release of SARS-CoV-2 Spike (S) antibodies in human milk samples obtained by patients who have been vaccinated with mRNABNT162b2 vaccine. Methods: Milk and serum samples were collected in 10 volunteers 20 days after the first dose and 7 seven days after the second dose of the mRNABNT162b2 vaccine. Anti-SARS-CoV-2 S antibodies were measured by the Elecsys^® Anti-SARS-CoV-2 S ECLIA assay (Roche Diagnostics AG, Rotkreuz, Switzerland), a quantitative electrochemiluminescence immunometric method. Results: At first sample, anti-SARS-CoV-2 S antibodies were detected in all serum samples (103.9 ± 54.9 U/mL) and only in two (40%) milk samples with a low concentration (1.2 ± 0.3 U/mL). At the second sample, collected 7 days after the second dose, anti-SARS-CoV-2 S antibodies were detected in all serum samples (3875.7 ± 3504.6 UI/mL) and in all milk samples (41.5 ± 47.5 UI/mL). No correlation was found between the level of serum and milk antibodies; the milk antibodies/serum antibodies ratio was on average 2% (range: 0.2–8.4%). Conclusion: We demonstrated a release of anti-SARS-CoV-2 S antibodies in the breast milk of women vaccinated with mRNABNT162b2. Vaccinating breastfeeding women could be a strategy to protect their infants from COVID-19 infection. Full article

Improving the immunogenicity and protective efficacy of vaccines is critical to reducing disease impacts. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to the antigen presenting cells (APCs). In this study, we have developed a targeted antigen delivery vaccine (TADV) system by recombinantly fusing the ectodomain of hemagglutinin (HA) antigen of H9N2 influenza A virus to single chain fragment variable (scFv) antibodies specific for the receptors expressed on chicken APCs; Dec205 and CD11c. Vaccination of chickens with TADV containing recombinant H9HA Foldon-Dec205 scFv or H9HA Foldon-CD11c scFv proteins elicited faster (as early as day 6 post primary vaccination) and higher anti-H9HA IgM and IgY, haemagglutination inhibition, and virus neutralisation antibodies compared to the untargeted H9HA protein. Comparatively, CD11c scFv conjugated H9HA protein showed higher immunogenic potency compared to Dec205 scFv conjugated H9HA protein. The higher immune potentiating ability of CD11c scFv was also reflected in ex-vivo chicken splenocyte stimulation assay, whereby H9HA Foldon-CD11c scFv induced higher levels of cytokines (IFNγ, IL6, IL1β, and IL4) compared to H9HA Foldon-Dec205 scFv. Overall, the results conclude that TADV could be a better alternative to the currently available inactivated virus vaccines. Full article

Background: This study aimed to explore behavioral-related factors predicting the intention of getting a COVID-19 vaccine among medical and nursing students using an integrative model combining the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB). Methods: A cross-sectional online survey was conducted among medical and nursing students aged > 18 years in their clinical years in Israel between 27 August and 28 September 2020. Hierarchical logistic regression was used to predict acceptance of a COVID-19 vaccine. Results: A total number of 628 participants completed the survey. Medical students expressed higher intentions of getting vaccinated against COVID-19 than nursing students (88.1% vs. 76.2%, p < 0.01). The integrated model based on HBM and TPB was able to explain 66% of the variance (adjusted R² = 0.66). Participants were more likely to be willing to get vaccinated if they reported higher levels of perceived susceptibility, benefits, barriers, cues to action, attitude, self-efficacy and anticipated regret. Two interaction effects revealed that male nurses had a higher intention of getting vaccinated than did female nurses and that susceptibility is a predictor of the intention of getting vaccinated only among nurses. Conclusions: This study demonstrates that both models considered (i.e., HBM and TPB) are important for predicting the intention of getting a COVID-19 vaccine among medical and nursing students, and can help better guide intervention programs, based on components from both models. Our findings also highlight the importance of paying attention to a targeted group of female nurses, who expressed low vaccine acceptance. Full article

A fusion chimeric vaccine comprising multiple protective domains of different blood-stage Plasmodium falciparum antigens is perhaps necessary for widening the protective immune responses and reducing the morbidity caused by the disease. Here we continue to build upon the prior work of developing a recombinant fusion chimera protein, His-tagged PfMSP-Fu24, by producing it as a tag-free recombinant protein. In this study, tag-free recombinant PfMSPFu24 (rFu24) was expressed in Escherichia coli, and the soluble protein was purified using a three-step purification involving ammonium sulphate precipitation followed by 2-step ion exchange chromatography procedures and shown that it was highly immunogenic with the human-compatible adjuvant Alhydrogel. We further investigated two dipeptides, phenylalanine-α, β-dehydrophenylalanine (FΔF) and Leucine-α, β-dehydrophenylalanine (LΔF) based hydrogels as effective delivery platforms for rFu24. These dipeptides self-assembled spontaneously to form a highly stable hydrogel under physiological conditions. rFu24 was efficiently entrapped in both the F∆F and L∆F hydrogels, and the three-dimensional (3D) mesh-like structures of the hydrogels remained intact after the entrapment of the antigen. The two hydrogels significantly stimulated rFu24-specific antibody titers, and the sera from the immunized mice showed an invasion inhibitory activity comparable to that of Alhydrogel. Easily synthesized dipeptide hydrogels can be used as an effective antigen delivery platform to induce immune responses. Full article

The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may particularly concern patients with a diminished immune response to the vaccine, as well as non-responders. This work has retrospectively analyzed the 92 cases of patients who were hospitalized between 27 December 2020 and 31 May 2021 in four Polish healthcare units due to COVID-19, and who have previously received the COVID-19 vaccine (54.3% ≤ 14 days after the first dose, 26.1% > 14 days after the first dose, 7.6% ≤ 14 days after the second dose, and 12% > 14 days after the second dose). These patients represented a minute fraction (1.2%) of all the COVID-19 patients who were hospitalized during the same period in the same healthcare institutions. No significant differences in white blood count, absolute lymphocyte count nadir, C-reactive protein, interleukin-6, procalcitonin, oxygen saturation, lung involvement, and fever frequency were found between the recipients of the first and second vaccine dose. A total of 15 deaths were noted (1.1% of all fatal COVID-19 cases in the considered period and healthcare units), including six in patients who received the second dose (five > 14 days after the second dose)—three of these subjects were using immunosuppressive medicines, and two were confirmed to be vaccine non-responders. The study reassures that severe COVID-19 and deaths are not common in vaccinated individuals, highlights that the clinical course in such patients may not reveal any distinctive features, and advocates for close monitoring of those at a higher risk of vaccine failure. Full article

The past 30 years have seen the growth of plant molecular farming as an approach to the production of recombinant proteins for pharmaceutical and biotechnological uses. Much of this effort has focused on producing vaccine candidates against viral diseases, including those caused by enveloped viruses. These represent a particular challenge given the difficulties associated with expressing and purifying membrane-bound proteins and achieving correct assembly. Despite this, there have been notable successes both from a biochemical and a clinical perspective, with a number of clinical trials showing great promise. This review will explore the history and current status of plant-produced vaccine candidates against enveloped viruses to date, with a particular focus on virus-like particles (VLPs), which mimic authentic virus structures but do not contain infectious genetic material. Full article

Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from “Sputnik V”-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow. Full article

For epidemiological studies of infectious diseases, pathogen-specific antibody levels in an area give us essential and appropriate information. The antibodies against pathogens are usually detected in blood, the drawing of which inconveniences people. Collection of blood increases the risk of accidental infections through blood, and it is difficult to obtain the participation of the target populations, especially the younger generation. On the other hand, urine samples, which contain a high enough level of antibodies for ELISA, can be harmlessly and easily collected and therefore have been used for epidemiological studies for diseases. The antibody examination of urine has been used for the epidemiology of parasitic diseases with a high sensitivity and specificity of serum samples. In this paper, we reviewed antibody assays with urine for seven parasitic diseases that urine diagnostic methods have reported in the past, and these are important infections included in NTDs, caused, for example, by Leishmania donovani, Wuchereria bancrofti, Schistosoma japonicum, Paragonimus westermani, Echinococcus granulosus, Echinococcus multilocularis, Strongyloides stercoralis, and Opisthorchis viverrini. The easy and safe urine surveillance system might be an admirable tool for future epidemiological studies for infectious diseases. Full article

Vaccination hesitancy is a threat to herd immunity. Healthcare workers (HCWs) play a key role in promoting Coronavirus disease 2019 (COVID-19) vaccination in the general population. We therefore aimed to provide data on COVID-19 vaccination acceptance/hesitancy among German HCWs. For this exploratory, cross-sectional study, an online survey was conducted in February 2021. The survey included 54 items on demographics; previous vaccination behavior; trust in vaccines, physicians, the pharmaceutical industry and health politics; fear of adverse effects; assumptions regarding the consequences of COVID-19; knowledge about vaccines; and information seeking behavior. Odds ratios with 95% confidence intervals were calculated and chi-square tests were performed. Four thousand five hundred surveys were analyzed. The overall vaccination acceptance was 91.7%. The age group ≤20 years showed the lowest vaccination acceptance. Factors associated with vaccination hesitancy were lack of trust in authorities and pharmaceutical companies. Attitudes among acquaintances were associated with vaccination hesitancy too. Participants with vaccination hesitancy more often obtained information about COVID-19 vaccines via messenger services or online video platforms and underperformed in the knowledge test. We found high acceptance amongst German HCWs. Several factors associated with vaccination hesitancy were identified which could be targeted in HCW vaccination campaigns. Full article

Introduction: Human papillomavirus (HPV) is associated with six types of cancer in men and women. A vaccine against HPV, preferably administered before initial sexual intercourse, has been proven to be highly effective in preventing these cancers. An effective healthcare provider recommendation has significant influence on HPV vaccine uptake; therefore, it is critical that medical students receive comprehensive training in this area. Aim: The aim of the study was to assess the knowledge of medical students regarding Human Papillomavirus’s (HPV) ways of transmission, risk of cancer development, and vaccination against HPV. This study also investigated factors among medical students that would affect their intention to recommend HPV vaccination to others. Materials and Methods: The study was conducted among 1061 (678 women and 383 men) medical students who filled in our questionnaire. The medical students were divided into two subgroups: (1) pre-clinical medical students (MS pre-clinical; first-to third-year students; n = 683) and (2) clinical medical students (MS clinical; fourth-to six-year students; n = 378). Results: A total259 (24.41%) of the 1061 medical students were vaccinated against HPV. We found a significant improvement in the general level of knowledge in the later years of education (4–6) compared to the early years of education (1–3). However, it was demonstrated that, despite medical education advancements, there are still significant gaps of knowledge about the relationship between HPV infection and cancers other than cervical cancer, as well as in relation to the routes by which HPV is transmitted. Medical students’ intentions to recommend HPV vaccine to others were related to their own HPV-related knowledge and their own vaccination status. Conclusion: Medical students have gaps of knowledge regarding particular issues and aspects of HPV. It is necessary to further educate medical students in the field of prevention and in the treatment of lesions caused by HPV infection. Medical students’ intention to recommend the HPV vaccine can be improved by including them and members of their families in the HPV vaccination program. Full article

A vaccine that effectively targets methicillin-resistant Staphylococcus aureus (MRSA) is urgently needed, and has been the focus of studies by numerous research groups, but with limited success to date. Recently, our team found that exopolysaccharides derived from probiotic Lactobacilluscasei strain WXD030 as an adjuvant-formulated OVA could upregulate IFN-γ and IL-17 expression in CD4⁺ T cells. In this study, we developed a vaccine (termed rMntC-EPS) composed of S. aureus antigen MntC and Lactobacillus casei exopolysaccharides, which conferred high levels of protection against S. aureus infection. Methods: Six–eight-week-old female mice were vaccinated with purified rMntC-EPS30. The immune protection function of rMntC-EPS30 was assessed by the protective effect of rMntC-EPS30 to S. aureus-induced pulmonary and cutaneous infection in mice, bacterial loads and H&E in injury site, and ELISA for inflammation-related cytokines. The protective mechanism of rMntC-EPS30 was assessed by ELISA for IgG in serum, cytokines in the spleen and lungs of vaccinated mice. In addition, flow cytometry was used for analyzing cellular immune response induced by rMntC-EPS30. For confirmation of our findings, three kinds of mice were used in this study: IL-17A knockout mice, IFN-γ knockout mice and TCRγ/δ knockout mice. Results: rMntC-EPS30 conferred up to 90% protection against S. aureus pulmonary infection and significantly reduced the abscess size in the S. aureus cutaneous model, with clearance of the pathogen. The rMntC-EPS vaccine could induce superior humoral immunity as well as significantly increase IL-17A and IFN-γ production. In addition, we found that rMntC-EPS vaccination induced robust Th 17/γδ T 17 primary and recall responses. Interestingly, this protective effect was distinctly reduced in the IL-17A knockout mice but not in IFN-γ knockout mice. Moreover, in TCRγ/δ knockout mice, rMntC-EPS vaccination neither increased IL-17A secretion nor provided effective protection against S. aureus infection. Conclusions: These data demonstrated that the rMntC formulated with a novel Lactobacillus-derived Exopolysaccharides adjuvant provided high protection against Staphylococcus aureus. The rMntC-EPS vaccine induced γδ T cells and IL-17A might play substantial roles in anti-S. aureus immunity. Our findings provided direct evidence that rMntC-EPS vaccine is a promising candidate for future clinical application against S. aureus-induced pulmonary and cutaneous infection. Full article