It is important to know the attitudes of students of health sciences (SHSs) towards vaccination since they will be tomorrow’s health professionals. Vaccination is a powerful tool in the fight against COVID-19. The aim of the present, cross-sectional study was to examine how the COVID-19 pandemic has influenced the attitude of SHSs towards vaccination. Data were collected in the form of a questionnaire from all students of nursing, physiotherapy and chiropody matriculated at a Madrid University for the academic year 2019/2020 (i.e., before the start of the pandemic [Q1]), and from all those matriculated for the year 2021/22 (i.e., c18 months after the pandemic was declared [Q2]). A multivariate analysis was performed to identify the influence of sex, degree being studied, course year and the time of answering (Q1 or Q2), on the dimensions Beliefs, Behaviours and General Attitude. Overall, 1894 questionnaires were returned (934 [49.3%] for Q1, and 960 [50.7%] for Q2), of which 70.5% were completed by students of nursing, 14% by students of physiotherapy and 15.4% by those studying chiropody. In Q2, the results for all three dimensions were significantly better (p < 0.05). The most important influencing factors were being a student of nursing, being in the final years of training (years 3 or 4), female gender and answering at the time of Q2. The results obtained are encouraging since student nurses (who showed Q1 and Q2 General Attitude scores of 3.34 and 3.47 (maximum possible 4), respectively [p < 0.05]) are the health professionals of tomorrow most likely to be involved in vaccination programmes. Full article

SARS-CoV-2 vaccine production has taken us by storm. We aim to fill in the history of concepts and the work of pioneers and provide a framework of strategies employing structural vaccinology. Cryo-electron microscopy became crucial in providing three-dimensional (3D) structures and creating candidates eliciting T and B cell-mediated immunity. It also determined structural changes in the emerging mutants in order to design new constructs that can be easily, quickly and safely added to the vaccines. The full-length spike (S) protein, the S1 subunit and its receptor binding domain (RBD) of the virus are the best candidates. The vaccine development to cease this COVID-19 pandemic sets a milestone for the pan-coronavirus vaccine’s designing and manufacturing. By employing structural vaccinology, we propose that the mRNA and the protein sequences of the currently approved vaccines should be modified rapidly to keep up with the more infectious new variants. Full article

Immune-escape hepatitis B virus (HBV) mutants play an important role in HBV spread. Recently, the multivalent vaccine Bubo^®-Unigep has been developed to protect against both wild-type HBV and the most significant G145R mutant. Here, we compared the effects of recombinant HBsAg antigens, wild-type and mutated at G145R, both included in the new vaccine, on activation of a human high-density culture of peripheral blood mononuclear cells (PBMC) in vitro. The antigens were used either alone or in combination with phytohemagglutinin (PHA). None of the antigens alone affected the expression of CD40, HLA-DR or CD279. Wild-type HBsAg enhanced CD86 and CD69 expression, and induced TNF-α, IL-10, and IFN-γ, regardless of the anti-HBsAg status of donor. In the presence of PHA, wild-type HBsAg had no effect on either of the tested surface markers, but increased IFN-γ and IL-10 and inhibited IL-2. In contrast, the G145R mutant alone did not affect CD86 expression, it induced less CD69, and stimulated IL-2 along with lowering levels of TNF-α, IL-10, and IFN-γ. The G145R mutant also suppressed PHA-induced activation of CD69. The dramatic differences in the immune responses elicited by wild-type HBsAg and the G145R mutant HBsAg suggest distinct adaptive capabilities of the G145R mutant HBV. Full article

BCG has shown the ability to induce protection against unrelated pathogens, which likely depends on an immune mechanism known as innate immune memory or trained immunity. In this study, we evaluated the induction of innate memory by a recombinant BCG strain expressing the genetically detoxified S1 subunit of the pertussis toxin (rBCG-S1PT). In vitro pre-exposure of naïve murine macrophages to rBCG-S1PT increased their innate/inflammatory response (IL-6, TNF-α, and IL-10) to a subsequent challenge with unrelated pathogens, as compared to pre-exposure to wild-type BCG. Following LPS challenge, mice immunized with rBCG-S1PT produced higher levels of IFN-γ, while the release of other inflammatory cytokines was comparable to that measured after BCG immunization. SCID mice previously immunized with rBCG-S1PT and challenged with pathogenic Candida albicans displayed a similar survival curve as BCG-immunized mice but a lower CFU burden in the kidneys, suggesting an innate memory-dependent control of C. albicans infection. This study highlights the potential of recombinant BCG to increase innate immune memory and, ultimately, non-specific protection, more effectively than wild-type BCG. To our knowledge, this is the first report describing the potential of a recombinant BCG strain to strengthen innate immune memory responses. Full article

Background: The adverse events reported from the COVID-19 mRNA vaccines have varied from very mild, such as pain near the vaccination site, to more severe, with occasional anaphylaxis. Details of age-specific gender differences for the adverse effects are not well documented. Methods: Age and gender disaggregated data on reports of adverse events following two or three doses of the Pfizer-BioNTech COVID-19 vaccine were obtained from four cross-sectional studies. The first was from reports submitted to the Israel Ministry of Health national adverse events database (for ages 16 and above). The second was from a national cross-sectional survey based on an internet panel (for ages 30 and above), and the third and fourth were from cross-sectional surveys among employees of a large company (for ages 20–65) using links to a self-completed questionnaire. Results: In all studies, the risks of adverse events were higher following the second dose and consistently higher in females at all ages. The increased risk among females at all ages included local events such as pain at the injection site, systemic events such as fever, and sensory events such as paresthesia in the hands and face. For the combined adverse reactions, for the panel survey the female-to-male risk ratios (RRs) were 1.89 for the first vaccine dose and 1.82 for the second dose. In the cross-sectional workplace studies, the female-to-male RRs for the first, second and third doses exceeded 3.0 for adverse events, such as shivering, muscle pain, fatigue and headaches. Conclusions: The consistent excess in adverse events among females for the mRNA COVID-19 vaccine indicates the need to assess and report vaccine adverse events by gender. Gender differences in adverse events should be taken into account when determining dosing schedules. Full article

To date, billions of vaccine doses have been administered to restrain the current COVID-19 pandemic worldwide. Rare side effects, including intravascular blood clots, were reported in the general population after vaccination. Among these, cerebral venous sinus thrombosis (CVST) has been considered the most serious one. To shed further light on such an event, we conducted a literature search for case descriptions of CVST in vaccinated people. Findings were analyzed with emphasis on demographic characteristics, type of vaccine, site of thrombosis, clinical and histopathological findings. From 258 potential articles published till September 2021, 41 studies were retrieved for a total of 552 patients. Of these, 492 patients (89.1%) had received AZD1222/Vaxzevria, 45 (8.2%) BNT162b2/CX-024414 Spikevax, 15 (2.7%) JNJ-78436735, and 2 (0.3%) Covishield vaccine. CVST occurred in 382 women and 170 men (mean aged 44 years), and the median timing from the shot was 9 days (range 2–45). Thrombi were predominantly seen in transverse (84%), sigmoid (66%), and/or superior sagittal (56%) sinuses. Brain injury (chiefly intracranial bleeding) occurred in 32% of cases. Of 426 patients with detailed clinical course, 63% were discharged in good clinical conditions, at times with variable neurological sequelae, whereas 37% deceased, largely due to brain injury. This narrative review confirmed CVST as a rare event after (adenoviral vector) COVID-19 vaccination, with a women/men rate ratio of 2.25. Though the pathogenesis of thrombosis is still under discussion, currently available histopathological findings likely indicate an underlying immune vasculitis. Full article

Leishmania parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different Leishmania species’ life-cycles and stage forms in regard to their distinct infective ability. Based on expression patterns, homology to human orthologues, in silico HLA-binding predictions, and annotated functions, we were able to select several vaccine candidates which are currently under study. One of these candidates is the Leishmania infantum ubiquitin-conjugating enzyme E2 (LiUBC1), whose relative levels, subcellular location, in vitro infectivity in the U937 myeloid human cell model, and protection levels in Syrian hamsters against L. infantum infection were studied herein. LiUBC1 displays a low level of similarity with the mammalian orthologs and relevant structure differences, such as the C-terminal domain, which is absent in the human ortholog. LiUBC1 is present in highly infective promastigotes. Knock-in parasites overexpressing the enzyme increased their infectivity, according to in vitro experiments. Syrian hamsters immunized with the recombinant LiUBC1 protein did not show any parasite burden in the spleen, unlike the infection control group. The IFN-γ transcript levels in splenocytes were significantly higher in the LiUBC1 immunized group. Therefore, LiUBC1 induced partial protection against L. infantum in the Syrian hamster model. Full article

COVID-19 vaccination hesitancy has become a major concern around the world. Recent reports have also highlighted COVID-19 vaccination hesitancy in healthcare workers. Despite media reports and scientific publications, little is known about the extent and predictors of COVID-19 vaccination refusal among nurses. Thus, the purpose of this study was to assess COVID-19 vaccine refusal rates among nurses globally and to explore the reasons for refusal and factors associated with the uptake of the vaccines. A scoping review of the published literature was conducted, and a final pool of 51 studies (n = 41,098 nurses) from 36 countries was included in this review. The overall pooled prevalence rate of COVID-19 vaccine refusal among 41,098 nurses worldwide was 20.7% (95% CI = 16.5–27%). The rates of vaccination refusal were higher from March 2020–December 2020 compared to the rates from January 2021–May 2021. The major reasons for COVID-19 vaccine refusal were concerns about vaccine safety, side effects, and efficacy; misinformation and lack of knowledge; and mistrust in experts, authorities, or pharmaceutical companies. The major factors associated with acceptance of the vaccines were: male sex, older age, and flu vaccination history. Evidence-based strategies should be implemented in healthcare systems worldwide to increase the uptake of COVID-19 vaccines among nurses to ensure their safety and the safety of their patients and community members. Full article

The rabbit hemorrhagic disease virus (RHDV) vaccine platform is a nanoparticle composed of 180 copies of the viral capsid protein, VP60, self-assembled into virus-like particles (VLPs). RHDV VLPs are able to accept the simultaneous incorporation of target epitopes at different insertion sites. The resulting chimeric RHDV VLPs displaying immunogenic foreign antigens have been shown to induce specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes in the mouse and pig models. In this study, we explored whether RHDV-based engineered VLPs can be developed as efficient multivalent vaccines co-delivering different foreign B-cell antigens. We generated bivalent chimeric RHDV VLPs displaying two model B-cell epitopes at different surface-exposed insertion sites, as well as the corresponding monovalent chimeric VLPs. The immunogenic potential of the bivalent chimeric VLPs versus the monovalent constructs was assessed in the mouse model. We found that the bivalent chimeric VLPs elicited a strong and balanced antibody response towards the two target epitopes tested, although slight reductions were observed in the levels of specific serum antibody titers induced by bivalent chimeric VLPs as compared with the corresponding monovalent constructs. These results suggest that RHDV VLPs could represent a promising platform for the development of efficient multivalent vaccines. Full article

HPV is one of the diseases of civilization that causes cervical cancer, among other diseases. For this reason, a vaccination program has been introduced worldwide for preadolescent, sexually inactive seronegative girls. However, the decision to vaccinate young girls must be made by the parents. In Poland, vaccinations are recommended but not financed by the government, which affects their choices, and there is insufficient knowledge of the diseases caused by genital HPV types. In addition, there are cultural, social, and even religious factors to be considered. Therefore, the aim of the study was to analyze the state of knowledge about HPV and HPV vaccines among parents. Two hundred and eighty-eight parents participated in the study, but only 180 of them declared that they had ever heard of HPV (62.5%). Therefore, only these parents completed the entire questionnaire consisting of 34 questions. The parents’ answers were analyzed with the Fisher’s and chi-squared tests. The study showed that parents’ knowledge of HPV and HPV vaccination in Poland is low (49.4% of correct answers). Parents’ attitudes were only influenced by knowledge and education and not by other parameters such as age, gender, place of residence, and the number of children. This study indicates that parents need to be educated about the threats of HPV and the possibilities of prophylactic vaccination. Full article

Virus-like particles (VLPs) are self-assembled viral protein complexes that mimic the native virus structure without being infectious. VLPs, similarly to wild type viruses, are able to efficiently target and activate dendritic cells (DCs) triggering the B and T cell immunities. Therefore, VLPs hold great promise for the development of effective and affordable vaccines in infectious diseases and cancers. Vaccine formulations based on VLPs, compared to other nanoparticles, have the advantage of incorporating multiple antigens derived from different proteins. Moreover, such antigens can be functionalized by chemical modifications without affecting the structural conformation or the antigenicity. This review summarizes the current status of preventive and therapeutic VLP-based vaccines developed against human oncoviruses as well as cancers. Full article

Salmonella enterica is an important foodborne pathogen. Commercial poultry are the main reservoirs of Salmonella enterica, leading to the contamination of food and outbreaks in humans. The vaccination of chickens is one of the most important strategies to reduce the number of Salmonella in poultry farms. Unfortunately, commercial vaccines have not been fully effective in controlling the spread and do not contain all the Salmonella serovars that circulate on farms. In this study, we evaluate a new, cochleate-based, trivalent injectable vaccine against S. Enteritidis, S. Typhimurium and S. Infantis, describing the vaccine security, capacity to induce specific anti-Salmonella serovar IgY and the gene expression of immune markers related to CD4 and CD8 T-cell-mediated immunity. Efficacy was evaluated through oral challenges performed separately for each Salmonella serotype. The efficacy and safety of the trivalent vaccine was proven under controlled conditions. The vaccine has no local or systemic reactions or adverse effects on poultry performance related to the vaccine. The vaccine provided significantly increased serum IgY titer levels, significantly reduced Salmonella CFU/g present in the cecum and an increased CD4+/CD8+ ratio in vaccinated animals when challenged with S. Infantis, S. Enteritidis and S. Typhimurium. These results indicate that this new trivalent vaccine does not generate adverse effects in poultry and produces an increase in neutralizing antibodies against the three Salmonella serovars. Full article

SARS-CoV-2-specific antibody responses are engendered in human milk after BNT162b2 vaccination. However, the emergence of variants of concern (VOCs) raises concerns about the specificity of and potential cross-protection mediated by milk antibody responses, which are crucial for passive immunity transferred from breastfeeding mothers to their infants. In this study, we collected milk samples at three different time points pre- and post-vaccination, and measured milk IgA antibody binding to the receptor binding domain (RBD) of the original Wuhan-Hu-1 strain, and the four VOCs, namely Alpha, Beta, Gamma and Delta. We report a significant level of anti-RBD IgA in milk collected at 4–6 weeks after the second dose of vaccination compared to pre-vaccination. We observed around a 30% reduction in binding to most VOCs, including the major circulating Delta variant, compared to the original Wuhan-Hu-1 strain. As COVID-19 vaccines may take some time to be approved for infants, these individuals remain at risk for severe disease and rely mainly on transferred passive immunity. Our findings support the current recommendations for vaccinating lactating women with the aim of transferring mucosal immunity to breastfeeding infants. Full article

The adult Vaccine Hesitancy Scale (aVHS) is valid and reliable for evaluating attitudes toward vaccine preventable diseases (VPDs). The aim of the present study was to evaluate the cross-cultural adaptation, reliability, and validity of the Italian version of the aVHS. After cross-cultural adaptation of the aVHS, internal consistency (IC), intra-class correlation (ICC), and content validity (S-CVI) were evaluated through a survey on 160 workers. Results of the ICC were analyzed on questionnaires administered twice at a distance of two months and revealed a satisfactory reproducibility (0.87). The IC of the aVHS was assessed by the Cronbach alpha coefficient test, with a result of 0.94, demonstrating an excellent IC reliability. The S-CVI calculated for the total scale was 0.97. The aVHS is a valid and reliable tool for evaluating vaccine hesitancy toward adult vaccinations. We suggest the use of this scale in upcoming surveys on opinions and perceptions of adult vaccinations. Full article

Background: Several different types of vaccines have been developed for the prevention of coronavirus disease (COVID-19). Despite several local and systemic side-effects to COVID-19 vaccination reported, the vaccines are still considered the best intervention to tackle the spread of the virus and reduce the severity of COVID-19 infection. However, the reported side-effects continue to have a crucial role in public confidence in the vaccine and its acceptance. This study aimed to investigate the short-term side-effects reported by the healthcare workers (HCWs) in Saudi Arabia after receiving the first dose of the Oxford/AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccine. Methods: A prospective cohort study was conducted among HCWs in the Jazan region of southwestern Saudi Arabia. Healthcare workers who had received the first dose of the COVID-19 vaccine and agreed to participate in the study were followed up for 3 weeks post vaccination through a weekly online survey. Information was collected on local and/or systemic side-effects reported following vaccine administration. Participants’ general and demographic information was also collected. Results: A total of 57.2% (250/437) of the HCWs who participated in this study reported at least one side-effect. Injection site pain and redness (80.0%), fever (73.2%), whole-body pain/fatigue (56.4%), and headache (48.8%) were the most commonly reported side-effects. Moreover, 12.4% of the participants who reported side-effects needed to see a physician, and only one female participant was admitted to the hospital. Multivariate regression analyses revealed that nationality (Saudi, adjusted odds ratio (aOR) = 3.65; 95% CI = 2.40, 5.55) and residency (Jazan governorate, aOR = 0.38; 95% CI = 0.15, 0.95) were the significant factors associated with reporting COVID-19 post-vaccination side-effects, while the number of reported side-effects was found to be significantly influenced by occupation (medical, aOR = 0.42; 95% CI = 0.26, 0.66; p < 0.001) and gender (female, aOR = 0.61; 95% CI = 0.38, 0.97; p = 0.038). Conclusions: Findings of the present study support the safety of the Oxford/AstraZeneca COVID-19 vaccine among HCWs in Saudi Arabia. All the reported side-effects were mild-to-moderate side-effects. The findings may help convince vaccine-hesitant individuals and skeptics to accept the COVID-19 vaccine. Full article