Vaccines

The emerging SARS-CoV-2 variants and waning vaccine-elicited immunity are two public health challenges that occurred simultaneously and synergistically during the summer of 2021 and led to a surging demand for COVID-19 vaccine booster dose (BD) rollout. This study aimed to evaluate the COVID-19 vaccine booster hesitancy (VBH) among Czech healthcare workers to explore the potential determinants of VBH. A national cross-sectional survey-based study was carried out between 3 and 11 November 2021, using an online self-administered questionnaire (SAQ) that explored the participants’ demographic characteristics, COVID-19 infection and vaccine anamneses, willingness to receive COVID-19 vaccine BD, and the psychosocial drivers of VBH. A total of 3454 HCW properly responded to the online SAQ, of which 80.9% were females, 30.3% were medical professionals, and 50.5% were ≤47 years old. Most of the participants were already inoculated against SARS-CoV-2 (95.2%), and BTN162b2 was the most commonly administered vaccine (90.7%). As the study sample was planned to represent the target population, it revealed a high level of BD acceptance (71.3%) among Czech HCW, while 12.2% were still hesitant and 16.6% were against the currently available BD. These results are consistent with other recent results from central Europe. Medical professional, male, and older participants were more likely to accept BD rather than allied health professional, female, and younger participants. The BDs’ perceived effectiveness against severe illness, symptomatic infection, and community transmission was a significant and strong predictor for BD acceptance, while the effectiveness against the circulating variants was not that important for our target population. The BDs’ perceived safety and ethical dilemmas of vaccine justice should be addressed sufficiently while communicating with HCW and other population groups. The altruistic reasons for BD acceptance, i.e., family protection, patient protection, and community health protection, underpin the recommendation of postponing the COVID-19 vaccine mandating in favour of stressing these altruistic concerns amid public health messaging. Full article

Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work. Full article

Age is among the most prominent risk factors for developing severe COVID-19 disease, and therefore older adults are a major target group for vaccination against SARS-CoV-2. This review focusses on age-associated aspects of COVID-19 vaccines and vaccination strategies, and summarizes data on immunogenicity, efficacy and effectiveness of the four COVID-19 vaccines, which are licensed in the US and/or Europe; namely, the two mRNA vaccines by BioNTech/Pfizer (BNT162b2) and Moderna (mRNA-1273), and the adenovector vaccines developed by AstraZeneca/University Oxford (ChAdOx1-nCoV-19, AZD1222) and Janssen/Johnson&Johnson (Ad26.COV2-S), respectively. After very high protection rates in the first months after vaccination even in the older population, effectiveness of the vaccines, particularly against asymptomatic infection and mild disease, declined at later time points and with the emergence of virus variants. Many high-income countries have recently started administration of additional doses to older adults and other high-risk groups, whereas other parts of the world are still struggling to acquire and distribute vaccines for primary vaccination. Other vaccines are available in other countries and clinical development for more vaccine candidates is ongoing, but a complete overview of COVID-19 vaccine development is beyond the scope of this article. Full article

Ensuring timely access to affordable vaccines has been acknowledged as a global public health priority, as also recently testified by the debate sparked during the COVID-19 pandemic. Effective vaccine procurement strategies are essential to reach this goal. Nevertheless, this is still a neglected research topic. A narrative literature review on vaccine procurement was conducted, by retrieving articles from four academic databases (PubMed/MEDLINE, Scopus, Embase, WebOfScience), ‘grey’ literature reports, and institutional websites. The aim was to clarify key concepts and definitions relating to vaccine procurement, describe main vaccine procurement methods, and identify knowledge gaps and future perspectives. A theoretical conceptual framework was developed of the key factors involved in vaccine procurement, which include quality and safety of the product, forecasting and budgeting, procurement legislation, financial sustainability, and plurality of manufacture, contracting, investment in training, storage and service delivery, monitoring and evaluation. This information can be useful to support policymakers during planning, implementation, and evaluation of regional and national vaccine procurement strategies and policies. Full article

Recommendations by health professionals are important for vaccines that are not included in national schedules. This study explored health professionals’ perspectives on recommending non-scheduled (user-fee) childhood vaccinations in China, identifying key influences on professionals’ interactions with caregivers. We conducted individual semi-structured interviews with 20 health professionals from three provinces in China and analyzed data thematically using deductive and inductive coding. Health professionals from all three provinces were uncomfortable about being perceived to encourage parents to accept vaccines that incurred a fee. They provided information about non-scheduled vaccines but emphasized parental autonomy in decision-making. Rural parents were less aware of unscheduled vaccines and health professionals were more likely to encourage parents living in more affluent areas to consider these vaccines; varicella vaccine was preferred by parents as a way of preventing school absence. Economic incentives for unscheduled vaccines were given to staff at most study sites, although the amount given varied widely. These variations meant that staff receiving lower incentives were not motivated to promote non-scheduled vaccines if their workload was high; on the contrary, those receiving higher incentives were more likely to promote these vaccines. Health professionals need more guidance on how to recommend unscheduled vaccines in an informative, positive and appropriate manner. It is evident that parents’ awareness of these vaccines, and their economic circumstances, influence vaccinators recommendation practice. Economic incentives prompted health professionals to recommend non-scheduled vaccines; however, the application of such staff incentives varied widely in China. To adopt appropriate economic incentives, professional organizations should develop protocols for the use of incentives that account for their influence on recommendation practices. Suitable recommendation policy needs to balance basic salaries with performance-based incentives, consider overall workload, and include monitoring and evaluation of economic incentives. Full article

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. The availability of prophylactic vaccines for high-risk types of human papillomavirus (HPV) infection represents an important advancement in the prevention of cervical cancer. In Jordan, the availability of the HPV vaccination is restricted to individuals who are willing to pay. The aim of the current study was to evaluate the willingness and attitude of female university students in health schools/faculties in Jordan to get HPV vaccination and their knowledge about the virus. A self-administered online questionnaire was distributed in October 2021, which comprised 27 items to evaluate HPV knowledge, history of HPV vaccination, intentions to get the HPV vaccine, and the reason(s) behind vaccine refusal for those who rejected vaccination. The study sample comprised 836 participants: medical students (39.7%), pharmacy students (26.0%), dental students (21.2%), and nursing students (13.2%). Only 524 participants had heard of HPV prior to the study (62.7%), of which 48.7% knew about the availability of HPV vaccines. The lowest level of HPV knowledge was observed among nursing students. Only 19/524 students reported a history of HPV vaccination (3.6%). The overall willingness to receive HPV vaccination if provided freely was 75.0%, while only 16.0% were willing to pay for the vaccine. The most common reason for HPV vaccine rejection was the perceived low risk to get HPV infection. Significantly higher intentions to get HPV vaccination were found among older participants and medical students. The embrace of vaccine conspiracy beliefs was associated with a significantly less willingness to get the HPV vaccination (p < 0.001). Dependence on the internet/social media as the source of HPV knowledge was associated with a significantly lower intention to get HPV vaccination (p = 0.002). The coverage of the HPV vaccination among female university students in health schools in Jordan appeared extremely low; however, three-fourths of the students who had heard of HPV were willing to receive the HPV vaccination if provided freely. Complacency appeared as a major factor for HPV vaccine rejection. Increasing the levels of knowledge and awareness of HPV infection and its association with cervical cancer through reliable sources is recommended. This can be helpful for the individual benefit of the students besides the potentially positive role they can play in community education. Countering vaccine conspiracy beliefs with proper education and awareness programs can be helpful to appraise the role of HPV vaccines in cancer prevention. Full article

Waning of the mumps virus (MuV)-specific humoral response after vaccination has been suggested as a cause for recent mumps outbreaks in vaccinated young adults, although it cannot explain all cases. Moreover, CD8⁺ T cells may play an important role in the response against MuV; however, little is known about the characteristics and dynamics of the MuV-specific CD8⁺ T-cell response after MuV infection. Here, we had the opportunity to follow the CD8⁺ T-cell response to three recently identified HLA-A2*02:01-restricted MuV-specific epitopes from 1.5 to 36 months post-MuV infection in five previously vaccinated and three unvaccinated individuals. The infection-induced CD8⁺ T-cell response was dominated by T cells specific for the ALDQTDIRV and LLDSSTTRV epitopes, while the response to the GLMEGQIVSV epitope was subdominant. MuV-specific CD8⁺ T-cell frequencies in the blood declined between 1.5 and 9 months after infection. This decline was not explained by changes in the expression of inhibitory receptors or homing markers. Despite the ongoing changes in the frequencies and phenotype of MuV-specific CD8⁺ T cells, TCRβ analyses revealed a stable MuV-specific T-cell repertoire over time. These insights in the maintenance of the cellular response against mumps may provide hallmarks for optimizing vaccination strategies towards a long-term cellular memory response. Full article

Mass immunization of the citizens of the Republic of Serbia began in January 2021. Information on the significance, manner, advantages and consequences of this process was intensively distributed through all communication channels, with the media playing a key role. According to the data of the official institutions for the public health of Serbia, by July 2021 the lowest percentage of vaccinated population was among those between the ages of 18 and 24—only 15% of this demographic had received the vaccine by this point. Given the low turnout of young people for vaccination, in this paper we investigated the general attitude of students in Serbia, as a special category of young people, towards the vaccine against the COVID-19 virus, as well as their attitude regarding information about vaccination in the media. Research was conducted on a sample of 345 students at the University of Novi Sad. The results of the research showed that 42% of students had not been vaccinated and did not plan to do so, 37.4% had received at least one dose of vaccine and 20.6% had not been vaccinated even though they planned to do so. Students who were vaccinated had more confidence in information provided through media channels than those who were not vaccinated. Therefore, it can be concluded that encouraging students to decide in favor of vaccination against the COVID-19 virus should come from the universities where they study as well as the media. Full article

In Alberta, infectious laryngotracheitis virus (ILTV) infection is endemic in backyard poultry flocks; however, outbreaks are only sporadically observed in commercial flocks. In addition to ILTV vaccine revertant strains, wild-type strains are among the most common causes of infectious laryngotracheitis (ILT). Given the surge in live attenuated vaccine-related outbreaks, the goal of this study was to assess the efficacy of a recombinant herpesvirus of turkey (rHVT-LT) vaccine against a genotype VI Canadian wild-type ILTV infection. One-day-old specific pathogen-free (SPF) White Leghorn chickens were vaccinated with the rHVT-LT vaccine or mock vaccinated. At three weeks of age, half of the vaccinated and the mock-vaccinated animals were challenged. Throughout the experiment, weights were recorded, and feather tips, cloacal and oropharyngeal swabs were collected for ILTV genome quantification. Blood was collected to isolate peripheral blood mononuclear cells (PBMC) and quantify CD4+ and CD8+ T cells. At 14 dpi, the chickens were euthanized, and respiratory tissues were collected to quantify genome loads and histological examination. Results showed that the vaccine failed to decrease the clinical signs at 6 days post-infection. However, it was able to significantly reduce ILTV shedding through the oropharyngeal route. Overall, rHVT-LT produced a partial protection against genotype VI ILTV infection. Full article

Nursing home residents (NHR) have been targeted as a vaccination priority due to their higher risk of worse outcome after COVID-19 infection. The mRNA-based vaccine BTN2b2 was first approved in Europe for NHRs. The assessment of the specific vaccine immune response (both humoral and cellular) at long term in NHRs has not been addressed yet. A representative sample of 624 NHR subjects in Northern region of Spain was studied to assess immune response against full vaccination with BTN2b2. The anti-S1 antibody levels and specific T cells were measured at two and six months after vaccination. 24.4% of NHR had a previous infection prior to vaccination. The remaining NHR were included in the full vaccination assessment group (FVA). After two months, a 94.9% of the FVA presented anti-S1 antibodies, whereas those seronegative without specific cellular response were 2.54%. At long-term, the frequency of NHR within the FVA group with anti-S1 antibodies at six months were 88.12% and the seronegative subjects without specific cellular response was 8.07%. The cellular immune assays complement the humoral test in the immune vaccine response assessment. Therefore, the cellular immune assessment in NHRs allows for the fine tuning of those seronegative subjects with potential competent immune responses against the vaccine. Full article

In this study, we evaluated the status of and attitudes toward COVID-19 vaccination of healthcare workers in two major hospital systems (academic and private) in Southern California. Responses were collected via an anonymous and voluntary survey from a total of 2491 participants, including nurses, physicians, other allied health professionals, and administrators. Among the 2491 participants that had been offered the vaccine at the time of the study, 2103 (84%) were vaccinated. The bulk of the participants were middle-aged college-educated White (73%), non-Hispanic women (77%), and nursing was the most represented medical occupation (35%). Political affiliation, education level, and income were shown to be significant factors associated with vaccination status. Our data suggest that the current allocation of healthcare workers into dichotomous groups such as “anti-vaccine vs. pro-vaccine” may be inadequate in accurately tailoring vaccine uptake interventions. We found that healthcare workers that have yet to receive the COVID-19 vaccine likely belong to one of four categories: the misinformed, the undecided, the uninformed, or the unconcerned. This diversity in vaccine hesitancy among healthcare workers highlights the importance of targeted intervention to increase vaccine confidence. Regardless of governmental vaccine mandates, addressing the root causes contributing to vaccine hesitancy continues to be of utmost importance. Full article

Cryptosporidium parvum (C. parvum) is a protozoan parasite known for cryptosporidiosis in pre-weaned calves. Animals and patients with immunosuppression are at risk of developing the disease, which can cause potentially fatal diarrhoea. The present study aimed to construct a network biology framework based on the differentially expressed genes (DEGs) of C. parvum infected subjects. In this way, the gene expression profiling analysis of C. parvum infected individuals can give us a snapshot of actively expressed genes and transcripts under infection conditions. In the present study, we have analyzed microarray data sets and compared the gene expression profiles of the patients with the different data sets of the healthy control. Using a network medicine approach to identify the most influential genes in the gene interaction network, we uncovered essential genes and pathways related to C. parvum infection. We identified 164 differentially expressed genes (109 up- and 54 down-regulated DEGs) and allocated them to pathway and gene set enrichment analysis. The results underpin the identification of seven significant hub genes with high centrality values: ISG15, MX1, IFI44L, STAT1, IFIT1, OAS1, IFIT3, RSAD2, IFITM1, and IFI44. These genes are associated with diverse biological processes not limited to host interaction, type 1 interferon production, or response to IL-gamma. Furthermore, four genes (IFI44, IFIT3, IFITM1, and MX1) were also discovered to be involved in innate immunity, inflammation, apoptosis, phosphorylation, cell proliferation, and cell signaling. In conclusion, these results reinforce the development and implementation of tools based on gene profiles to identify and treat Cryptosporidium parvum-related diseases at an early stage. Full article

Systemic sclerosis (SSc) is a rare autoimmune inflammatory rheumatic disease. The prevalence of SSc ranges from 7 to 700 cases per million worldwide. Due to multiple organ involvement and constant inflammatory state, this group of patients presents an increased risk of infectious diseases. This paper aimed to gather the up-to-date evidence on vaccination strategies for patients with SSc and to be a useful tool for the prevention and management of infectious diseases. The authors conducted a scoping review in which each paragraph presents data on a specific vaccine’s safety, immunogenicity, and efficacy. The work deals with the following topics: SARS-CoV-2, seasonal influenza, S. pneumoniae, HAV, HBV, HZV, N. meningitidis, H. influenzae, HPV, and diphtheria-tetanus-pertussis. Full article

Given the emergence of breakthrough infections, new variants, and concerns of waning immunity from the primary COVID-19 vaccines, booster shots emerged as a viable option to shore-up protection against COVID-19. Following the recent authorization of vaccine boosters among vulnerable Americans, this study aims to assess COVID-19 vaccine booster hesitancy and its associated factors in a nationally representative sample. A web-based 48-item psychometric valid survey was used to measure vaccine literacy, vaccine confidence, trust, and general attitudes towards vaccines. Data were analyzed through Chi-square (with a post hoc contingency table analysis) and independent-sample t-/Welch tests. Among 2138 participants, nearly 62% intended to take booster doses and the remaining were COVID-19 vaccine booster hesitant. The vaccine-booster-hesitant group was more likely to be unvaccinated (62.6% vs. 12.9%) and did not intend to have their children vaccinated (86.1% vs. 27.5%) compared to their non-hesitant counterparts. A significantly higher proportion of booster dose hesitant individuals had very little to no trust in the COVID-19 vaccine information given by public health/government agencies (55% vs. 12%) compared to non-hesitant ones. The mean scores of vaccine confidence index and vaccine literacy were lower among the hesitant group compared to the non-hesitant group. Compared to the non-hesitant group, vaccine hesitant participants were single or never married (41.8% vs. 28.7%), less educated, and living in a southern region of the nation (40.9% vs. 33.3%). These findings underscore the need of developing effective communication strategies emphasizing vaccine science in ways that are accessible to individuals with lower levels of education and vaccine literacy to increase vaccination uptake. Full article

Vaccination of cattle and buffaloes with Brucella abortus strain 19 has been the mainstay for control of bovine brucellosis. However, vaccination with S19 suffers major drawbacks in terms of its safety and interference with serodiagnosis of clinical infection. Brucella abortus S19∆per, a perosamine synthetase wbkB gene deletion mutant, overcomes the drawbacks of the S19 vaccine strain. The present study aimed to evaluate the potential of Brucella abortus S19Δper vaccine candidate in the natural host, buffaloes. Safety of S19∆per, for animals use, was assessed in guinea pigs. Protective efficacy of vaccine was assessed in buffaloes by immunizing with normal dose (4 × 10¹⁰ colony forming units (CFU)/animal) and reduced dose (2 × 10⁹ CFU/animal) of S19Δper and challenged with virulent strain of B. abortus S544 on 300 days post immunization. Bacterial persistency of S19∆per was assessed in buffalo calves after 42 days of inoculation. Different serological, biochemical and pathological studies were performed to evaluate the S19∆per vaccine. The S19Δper immunized animals showed significantly low levels of anti-lipopolysaccharides (LPS) antibodies. All the immunized animals were protected against challenge infection with B. abortus S544. Sera from the majority of S19Δper immunized buffalo calves showed moderate to weak agglutination to RBPT antigen and thereby, could apparently be differentiated from S19 vaccinated and clinically-infected animals. The S19Δper was more sensitive to buffalo serum complement mediated lysis than its parent strain, S19. Animals culled at 6-weeks-post vaccination showed no gross lesions in organs and there was comparatively lower burden of infection in the lymph nodes of S19Δper immunized animals. With attributes of higher safety, strong protective efficacy and potential of differentiating infected from vaccinated animals (DIVA), S19Δper would be a prospective alternate to conventional S19 vaccines for control of bovine brucellosis as proven in buffaloes. Full article

As COVID-19 remains an issue in transplantation medicine, a successful vaccination can prevent infections and life-threatening courses. The probability of poor immune response in liver transplant recipients gained attention and insecurity among those patients, leading us to investigate the humoral immune response alongside the influence of underlying diseases and immunosuppressive regimen on seroconversion rates. We included 118 patients undergoing anti-spike-protein-IgG testing at least 21 days after completed SARS-CoV-2 vaccination. Ninety-seven patients also underwent anti-spike-protein-IgA testing. The influence of baseline demographics, immunosuppressive regimen and underlying disease on seroconversion was analyzed, and 92 of 118 patients (78.0%) developed anti-spike-protein-IgG antibodies. Patients with a history of alcoholic liver disease before transplantation showed significantly lower seroconversion rates (p = 0.006). Immunosuppression also significantly influenced antibody development (p < 0.001). Patients run on a mycophenolate mofetil (MMF)-based regimen were more likely not to develop antibodies compared to patients run on a non-MMF regimen (p < 0.001). All patients weaned off immunosuppression were seropositive. The seroconversion rate of 78.0% in our cohort of liver transplant recipients is promising. The identification of alcohol-induced cirrhosis as underlying disease and MMF for immunosuppression as risk factors for seronegativity may serve to identify vaccination non-responder after liver transplantation. Full article

To protect against COVID-19, SARS-CoV-2 vaccines have been widely used. Besides anaphylaxis, some less severe adverse effects may occur at higher frequencies. It remains unclear whether present or past histories of allergic diseases exert effects on local and systemic reactions. We conducted a questionnaire survey among workers in our hospital. We analyzed the adverse effects occurring after the first and second doses of the Pfizer–BioNTech vaccine in 955 subjects. The presence or absence of local injection reactions and systemic reactions (headache, fatigability, fever, muscle pain, and joint pain) was questioned. The intensities of these reactions were graded on a scale of 0–4 (except fever) or 0–2 (fever). The allergic diseases that we focused on were bronchial asthma, atopic dermatitis, food allergy, pollinosis, and hand eczema. For the systemic reactions, fatigability after the first dose tended to be more severe in the bronchial asthma than in the non-allergic group. Headache, joint pain, and fever tended to be more severe in the food allergy than in the non-allergic group after the second dose. For the local skin reactions, atopic dermatitis subjects tended to show rather less severe local skin reactions after the second dose. The results contribute to the guidelines for the care of individuals with different allergy histories, so that they may safely receive their vaccine. Full article

The World Health Organization estimates that the pandemic caused by the SARS-CoV-2 virus claimed more than 3 million lives in 2020 alone. This situation has highlighted the importance of vaccination programs and the urgency of working on new technologies that allow an efficient, safe, and effective immunization. From this perspective, nanomedicine has provided novel tools for the design of the new generation of vaccines. Among the challenges of the new vaccine generations is the search for alternative routes of antigen delivery due to costs, risks, need for trained personnel, and low acceptance in the population associated with the parenteral route. Along these lines, transdermal immunization has been raised as a promising alternative for antigen delivery and vaccination based on a large absorption surface and an abundance of immune system cells. These features contribute to a high barrier capacity and high immunological efficiency for transdermal immunization. However, the stratum corneum barrier constitutes a significant challenge for generating new pharmaceutical forms for transdermal antigen delivery. This review addresses the biological bases for transdermal immunomodulation and the technological advances in the field of nanomedicine, from the passage of antigens facilitated by devices to cross the stratum corneum, to the design of nanosystems, with an emphasis on the importance of design and composition towards the new generation of needle-free nanometric transdermal systems. Full article

Many of the approved SARS-CoV-2 vaccines are based on a stabilized variant of the spike protein. This raises the question of whether the immune response against the stabilized spike is identical to the immune response that is elicited by the native spike in the case of a SARS-CoV-2 infection. Using a peptide array-based approach, we analysed the binding of antibodies from Comirnaty-elicited, convalescent, and control sera to the peptides covering the spike protein. A total of 37 linear epitopes were identified. A total of 26 of these epitopes were almost exclusively recognized by the convalescent sera. Mapping these epitopes to the spike structures revealed that most of these 26 epitopes are masked in the pre-fusion structure. In particular, in the conserved central helix, three epitopes that are only exposed in the post-fusion conformation were identified. This indicates a higher spike-specific antibody diversity in convalescent sera. These differences could be relevant for the breadth of spike-specific immune response. Full article