Vaccines, Volume 11, Issue 7 (July 2023) – 149 articles

African swine fever virus (ASFV) is the etiological agent of a haemorrhagic disease that threatens the global pig industry. There is an urgency to develop a safe and efficient vaccine, but the knowledge of the immune–pathogenetic mechanisms behind ASFV infection is still very limited. In this paper, we evaluated the haematological and immunological parameters of domestic pigs vaccinated with the ASFV Lv17/WB/Rie1 strain or its derived mutant Lv17/WB/Rie1/d110-11L and then challenged with virulent Armenia/07 ASFV. Circulating levels of C-reactive protein (CRP), 13 key cytokines and 11 haematological parameters were evaluated throughout the study. Lv17/WB/Rie1 triggered an inflammatory response, with increased levels of CRP and pro-inflammatory cytokines, and induced lymphopenia, thrombocytopenia and a decline in red blood cell (RBC) parameters, although this was transitory. Lv17/WB/Rie1/d110-11L triggered only transitory thrombocytopenia and a mild inflammatory reaction, with no increase in serum levels of pro-inflammatory cytokines, but it raised IL-1Ra levels. Both strains counteracted several adverse reactions elicited by virulent challenge, like thrombocytopenia, a decline in RBC parameters, and inflammation. Within this paper, we provided a deep portrayal of the impact of diverse ASFV strains on the domestic pig’s immune system. A better understanding of these immune–pathological mechanisms would help to design suitable vaccines against this disease. Full article

COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was first approved in Saudi Arabia in December 2020. Vaccinated individuals are still at risk of getting infected with the virus and can transmit the disease. Therefore, the perception of vaccinated individuals regarding the disease can help limit the spread of the virus. Objectives: To measure the risk perception of COVID-19 following vaccination and factors that have an effect on risk perception; to identify the health protective behaviours of the vaccinated individuals. Methodology: This is a quantitative analytical cross-sectional, questionnaire-based study. The target population includes individuals aged 18 and above who live in the Riyadh region and have been vaccinated, during the period of June 2021 to December 2021. Results: The perception of 30.2% of participants did not change after vaccination, with many participants continuing to “always” take precautions even after vaccination. Numerous factors, such as age, gender, marital status, occupational status, employment status, and total household income, have shown significant effects towards risk perception. Conclusion: Many vaccinated individuals have continued to take precautionary steps and their risk perception has not changed. Full article

Intracranial sarcoma is an uncommon aggressive cancer with a poor prognosis and a high recurrence rate. Although postoperative adjuvant radiotherapy (RT) is the most recommended treatment strategy, it does not significantly improve survival rates. In this study, we used an attenuated Salmonella typhimurium strain engineered to secrete Vibrio vulnificus flagellin B (SLpFlaB) as an immunotherapy to assist with the antitumor effects of RT on intracranial sarcoma. In vitro, the expression of γH2AX and cleaved caspase-3 was analyzed by Western blot. In vivo detection of SLpFlaB colonization time in tumors was measured using an in vivo imaging system (IVIS). Tumor growth delay and elimination were demonstrated in an intracranial mouse model, and the distribution of macrophages, M1 macrophages, and CD8⁺ cells after treatment was measured using FACS analysis. Our findings in vitro suggest that combination therapy increases S-180 radiosensitivity, the expression of DNA double-strand breaks, and programmed cell death. In vivo, combination treatment causes intracranial sarcoma to be eliminated without tumor recurrence and redistribution of immune cells in the brain, with data showing the enhanced migration and infiltration of CD8⁺ T cells and macrophages, and an increased proportion of M1 macrophage polarization. Compared to RT alone, the combination therapy enhanced the radiosensitivity of S-180 cells, promoted the recruitment of immune cells at the tumor site, and prevented tumor recurrence. This combination therapy may provide a new strategy for treating intracranial sarcomas. Full article

Background: Coverage rates of routinely recommended vaccines in older adults still fall below the targets established by international and national advisory committees. As a result, related diseases still have a high incidence, morbidity, and mortality. Information and Communication Technologies (ICT) could provide useful tools to improve immunization rates by bringing information directly to the target user at a relatively low cost. The present research aims to systematically review recent literature on interventions applying ICT to improve the uptake of influenza, pneumococcal, COVID-19 and herpes zoster immunization rates among older adults. Methods: Studies published in English between 1 January 2000 and 10 November 2022 were identified by searching electronic medical databases (PubMed, Scopus) and were independently reviewed by two different authors. A total of 22 studies were included in this review. Findings: Interventions applied the following ICT tools: phone calls, text messages, messages sent via personal electronic medical records, automated phone calls, remote patient monitoring in a home telehealth program and emails. In terms of the vaccines promoted, 11 studies prompted the influenza vaccine, four prompted the influenza and pneumococcal vaccines, three the pneumococcal vaccine, two the herpes zoster vaccine, one the COVID-19 vaccine and one both the pneumococcal and herpes zoster vaccines. Overall, more than half of the studies (n = 12) found some level of effectiveness of these ICT strategies in increasing vaccination rates among older adults, while five studies were partially effective (for specific vaccines or population subgroups), and five reported no significant effect. Conclusions: Prevention programs using ICT tools could be effective in promoting immunizations among older adults. Full article

Background: Brucella abortus is the main causative agent for bovine brucellosis. B. abortus A19 is a widely used vaccine strain to protect cows from Brucella infection in China. However, A19 has a similar lipopolysaccharide (LPS) antigen to that of the field virulent Brucella strain, whose immunization interferes with the serodiagnosis of vaccinated and infected animals. [Aim] To develop a novel Brucella DIVA vaccine candidate. Study design and methods: The B. abortus mutant A19mut2 with the formyltransferase gene wbkC is replaced by an acetyltransferase gene wbdR from E. coli O157 using the bacterial homologous recombination technique, generating a modified O-polysaccharide that cannot induce antibodies in mice against wild-type Brucella LPS. The biological phenotypes of the A19mut2 were assessed using a growth curve analysis, agglutination tests, Western blotting, and stress resistance assays. Histopathological changes and bacterial colonization in the spleens of vaccinated mice were investigated to assess the residual virulence and protection of the A19mut2. Humoral and cellular immunity was evaluated by measuring the levels of IgG, IgG subtypes, and the release of cytokines IFN-γ and IL10 in the splenocytes of the vaccinated mice. ELISA coated with wild-type LPS can distinguish mouse antibodies induced by A19 and A19mut2 immunization. Results: The A19mut2 showed a decreased residual virulence in mice, compared to the A19 strain, but induced significant humoral and cellular immune responses, as the A19 immunization did. The protection efficacy of A19mut2 immunization against B. abortus S2308 Nal^R infection was similar to that of A19 immunization. Conclusion: The A19mut2 has potential as a novel DIVA vaccine candidate in the future. Full article

We used three rounds of a repeated cross-sectional survey on COVID-19 vaccination conducted throughout the entire territory of Yemen to: (i) describe the demographic and socio-economic characteristics associated with willingness to be vaccinated; (ii) analyse the link between beliefs associated with COVID-19 vaccines and willingness to be vaccinated; and (iii) analyse the potential platforms that could be used to target vaccine hesitancy and improve vaccine coverage in Yemen. Over two-thirds of respondents were either unwilling or unsure about vaccination across the three rounds. We found that gender, age, and educational attainment were significant correlates of vaccination status. Respondents with better knowledge about the virus and with greater confidence in the capacity of the authorities (and their own) to deal with the virus were more likely to be willing to be vaccinated. Consistent with the health belief model, practising one (or more) COVID-19 preventative measures was associated with a higher willingness to get a COVID-19 vaccination. Respondents with more positive views towards COVID-19 vaccines were also more likely to be willing to be vaccinated. By contrast, respondents who believed that vaccines are associated with significant side effects were more likely to refuse vaccination. Finally, those who relied on community leaders/healthcare workers as a trusted channel for obtaining COVID-19-related information were more likely to be willing to be vaccinated. Strengthening the information about the COVID-19 vaccination (safety, effectiveness, side effects) and communicating it through community leaders/healthcare workers could help increase the COVID-19 vaccine coverage in Yemen. Full article

The hepatitis A virus (HAV) is still a leading cause of viral hepatitis worldwide. After a long incubation period, the clinical manifestations range from asymptomatic infection to acute liver failure. The severity of the disease increases with age and pre-existing liver disease. The transmission is mainly via person-to-person contact or ingestion of contaminated food or water. Food contamination can occur at any step of the food chain, especially when infected people handle not-heated or otherwise-treated food. HAV is endemic in low-income countries because of poor sanitary and sociodemographic conditions. The populations of developed countries are highly susceptible, and large outbreaks occur when HAV is introduced from endemic countries due to globalization, travel, and movement of foodstuffs. HAV prevention includes hygiene practices, immunoglobulins, and vaccination. Safe and effective inactivated and live attenuated vaccines are available and provide long-term protection. The vaccine targets are children and subjects at increased risk of HAV exposure or serious clinical outcomes. This review discusses the critical role of food handlers in the spread of HAV and the opportunity for food industry employers to consider food handler immunization a tool to manage both food safety in compliance with HACCP principles and food operators’ biologic risk. Full article

Human papilloma virus (HPV) vaccination rates remain below national goals in the United States despite the availability of evidence-based strategies to increase rates. The Adolescent Vaccination Program (AVP) is a multi-component intervention demonstrated to increase HPV vaccination rates in pediatric clinics through the implementation of six evidence-based strategies. The purpose of this study, conducted in Houston, Texas, from 2019–2021, was to adapt the AVP into an online decision support implementation tool for standalone use and to evaluate its feasibility for use in community clinics. Phase 1 (Adaptation) comprised clinic interviews (n = 23), literature review, Adolescent Vaccination Program Implementation Tool (AVP-IT) design documentation, and AVP-IT development. Phase 2 (Evaluation) comprised usability testing with healthcare providers (HCPs) (n = 5) and feasibility testing in community-based clinics (n = 2). AVP-IT decision support provides an Action Plan with tailored guidance on implementing six evidence-based strategies (immunization champions, assessment and feedback, continuing education, provider prompts, parent reminders, and parent education). HCPs rated the AVP-IT as acceptable, credible, easy, helpful, impactful, and appealing (≥80% agreement). They rated AVP-IT supported implementation as easier and more effective compared to usual practice (p ≤ 0.05). The clinic-based AVP-IT uses facilitated strategy implementation by 3-month follow-up. The AVP-IT promises accessible, utilitarian, and scalable decision support on strategies to increase HPV vaccination rates in pediatric clinic settings. Further feasibility and efficacy testing is indicated. Full article

Introduction: H5N1 is a highly pathogenic avian influenza virus that can infect humans and has an estimated fatality rate of 53%. As shown by the current situation of the COVID-19 pandemic, emerging and re-emerging viruses such as H5N1 have the potential to cause another pandemic. Thus, this study outlined the hub genes and pathways associated with H5N1 infection in humans. Methods: The genes associated with H5N1 infection in humans were retrieved from the NCBI Gene database using “H5N1 virus infection” as the keyword. The genes obtained were investigated for protein–protein interaction (PPI) using STRING version 11.5 and studied for functional enrichment analysis using DAVID 2021. Further, the PPI network was visualised and analysed using Cytoscape 3.7.2, and the hub genes were obtained using the local topological analysis method of the cytoHubba plugin. Results: A total of 39 genes associated with H5N1 infection in humans significantly interacted with each other, forming a PPI network with 38 nodes and 149 edges modulating 74 KEGG pathways, 76 biological processes, 13 cellular components, and 22 molecular functions. Further, the PPI network analysis revealed that 33 nodes interacted, forming 1056 shortest paths at 0.282 network density, along with a 1.947 characteristic path length. The local topological analysis predicted IFNA1, IRF3, CXCL8, CXCL10, IFNB1, and CHUK as the critical hub genes in human H5N1 infection. Conclusion: The hub genes associated with the H5N1 infection and their pathways could serve as diagnostic, prognostic, and therapeutic targets for H5N1 infection among humans. Full article

Tetanus toxoid (TT) vaccination during pregnancy has been proven as an effective preventative measure to reduce the incidence of maternal and neonatal morbidity and mortality worldwide. This study aimed to assess the determinants of TT vaccine uptake among pregnant women at two public maternity specialized hospitals in Sudan. A hospital-based cross-sectional study was conducted at two public hospitals, Omdurman Maternity Hospital and Al Saudi Hospital in Omdurman, Khartoum State, in Sudan from February to April 2020. Logistic regression analysis was carried out to identify factors associated with receiving three or more doses of the TT vaccine among pregnant women, presented as odds ratios, with p-values < 0.05 considered significant (at a 95% confidence interval). The study recruited 350 pregnant women, with 313 participants included in the analysis. This study found that only 40% of the pregnant women had received three doses or more of the TT vaccine. Pregnant women who attended Al Saudi Hospital were less likely to be vaccinated with the recommended dose of the TT vaccine in districts at high risk (received ≥3 doses) compared to those who attended Omdurman Hospital [OR = 0.49 (95% C.I. 0.29–0.82), p-value < 0.05]. Furthermore, the number of children at home was a significant predictor of the mothers’ immunization status as those with five children or more were ten times more likely to be vaccinated with three doses or more [OR = 10.54 (95% C.I. 4.30–25.86), p-value < 0.05]. We conclude that this low rate of TT vaccine uptake found in this study among pregnant women increases the number of newborn babies susceptible to contracting neonatal tetanus. The findings of this study should be considered in the development of communication strategies targeting and prioritizing at-risk groups to increase TT vaccine uptake among pregnant women in Sudan. Full article

Rhipicephalus microplus economically impacts cattle production in tropical and subtropical countries. Application of acaricides constitutes the major control method; however, inadequate use has increased resistant tick populations, resulting in environmental and cattle product contamination. Anti-tick vaccines based on the Bm86 antigen are an environmentally friendly, safe, and economically sustainable alternative for controlling R. microplus infestations. Nevertheless, variable efficacy has been experienced against different geographic tick strains. Herein, we evaluated the efficacy of a conserved polypeptide Bm86 derived from a Mexican R. microplus strain previously characterized. Twelve cows were assigned to three experimental groups and immunized with three doses of the polypeptide Bm86 (pBm86), adjuvant/saline alone, and Bm86 antigen (control +), respectively. Specific IgG antibody levels were measured by ELISA and confirmed by Western blot. In addition, the reproductive performance of naturally infested R. microplus was also determined. The more affected parameter was the adult female tick number, with a reduction of 44% by the pBm86 compared to the controls (p < 0.05), showing a vaccine efficacy of 58%. Anti-pBm86 IgG antibodies were immunogenic and capable of recognizing the native Bm86 protein in the eggs, larvae, and guts of R. microplus. The negative correlation between antibody levels and the reduction of naturally tick-infested cattle suggested that the effect of the polypeptide Bm86 was attributed to the antibody response in immunized cattle. In conclusion, the polypeptide Bm86 showed a specific immune response in cattle and conferred protection against R. microplus in a Mexican tropical region. These findings support further experiments with this antigen to demonstrate its effectiveness as a regional vaccine. Full article

The threat of bacterial septicemia caused by Aeromonas hydrophila infection to aquaculture growth can be prevented through vaccination, but differences among A. hydrophila strains may affect the effectiveness of non-conserved subunit vaccines or non-inactivated A. hydrophila vaccines, making the identification and development of conserved antigens crucial. In this study, a bioinformatics analysis of 4268 protein sequences encoded by the A. hydrophila J-1 strain whole genome was performed based on reverse vaccinology. The specific analysis included signal peptide prediction, transmembrane helical structure prediction, subcellular localization prediction, and antigenicity and adhesion evaluation, as well as interspecific and intraspecific homology comparison, thereby screening the 39 conserved proteins as candidate antigens for A. hydrophila vaccine. The 9 isolated A. hydrophila strains from diseased fish were categorized into 6 different molecular subtypes via enterobacterial repetitive intergenic consensus (ERIC)-PCR technology, and the coding regions of 39 identified candidate proteins were amplified via PCR and sequenced to verify their conservation in different subtypes of A. hydrophila and other Aeromonas species. In this way, conserved proteins were screened out according to the comparison results. Briefly, 16 proteins were highly conserved in different A. hydrophila subtypes, of which 2 proteins were highly conserved in Aeromonas species, which could be selected as candidate antigens for vaccines development, including type IV pilus secretin PilQ (AJE35401.1) and TolC family outer membrane protein (AJE35877.1). The present study screened the conserved antigens of A. hydrophila by using reverse vaccinology, which provided basic foundations for developing broad-spectrum protective vaccines of A. hydrophila. Full article

Introduction: French Guiana is a French territory bordering Brazil and Suriname where the COVID-19 pandemic has severely strained the French Guianese health system. The people working on illegal gold mining sites in French Guiana, also known as garimpeiros, are mainly of Brazilian origin. Their health conditions are precarious, they live under the radar of the surveillance system and therefore, assessment of their health is quite challenging.. The objective of this study was to describe their knowledge, attitudes and practices regarding COVID-19 and vaccination against this infection. Methods: We conducted an international multicenter cross-sectional survey between 1 March 2022 and 30 April 2022 in French Guiana and Suriname, using a structured questionnaire. Results: Eighty persons were included, 95.0% of whom were Brazilian. Most had good general knowledge of COVID-19. Antibiotic prophylaxis had been practiced by 10.0% of participants. Forty-three people thought they had been infected with COVID-19 (53.8%). Self-medication was frequent, often with antibiotics (32.6%, mostlychloroquine, ivermectin or azithromycin) and most had not consulted a physician for symptoms of COVID-19. A majority (62.5%) had received at least one dose of vaccine. Those who were ever tested for COVID-19 were the most likely to be vaccinated (PR = 1.98, p = 0.009). Conclusions: Garimpeiros have a good level of knowledge about COVID-19 but the high consumption of antibiotics raises concerns about the selection of resistant bacteria. The vaccination rate was higher than that of the Guianese population. The most vaccinated individuals were those who had already taken a COVID test suggesting that these individuals had more exposure to the disease, were more health conscious, or had easier access to health centers. Full article

The clinical use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria, leading to the current antibiotic resistance crisis. To address this issue, next-generation vaccines are being developed to prevent antimicrobial resistance caused by MDR bacteria. Traditional vaccine platforms, such as inactivated vaccines (IVs) and live attenuated vaccines (LAVs), were effective in preventing bacterial infections. However, they have shown reduced efficacy against emerging antibiotic-resistant bacteria, including MDR M. tuberculosis. Additionally, the large-scale production of LAVs and IVs requires the growth of live pathogenic microorganisms. A more promising approach for the accelerated development of vaccines against antibiotic-resistant bacteria involves the use of in silico immunoinformatics techniques and reverse vaccinology. The bioinformatics approach can identify highly conserved antigenic targets capable of providing broader protection against emerging drug-resistant bacteria. Multi-epitope vaccines, such as recombinant protein-, DNA-, or mRNA-based vaccines, which incorporate several antigenic targets, offer the potential for accelerated development timelines. This review evaluates the potential of next-generation vaccine development based on the reverse vaccinology approach and highlights the development of safe and immunogenic vaccines through relevant examples from successful preclinical and clinical studies. Full article

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population. Full article

Tilapia, as one of the fish widely cultured around the world, is suffering severe impact from the streptococcus disease with the deterioration of the breeding environment and the increasing of breeding density, which brings serious economic loss to tilapia farming. In this study, the surface immunogenic protein (Sip) of Streptococcus agalactiae (S. agalactiae) was selected as the potential candidate antigen and connected with bacterial nano cellulose (BNC) to construct the nanocarrier subunit vaccine (BNC-rSip), and the immersion immune effects against S. agalactiae and Streptococcus iniae (S. iniae) in Nile tilapia were evaluated on the basis of the serum antibody level, non-specific enzyme activity, the immune-related gene expression and relative percent survival (RPS). The results indicated that Sip possessed the expected immunogenicity according to the immunoinformatic analysis. Compared with the rSip group, BNC-rSip significantly induced serum antibody production and improved the innate immunity level of tilapia. After challenge, the RPS of BNC-rSip groups were 78.95% (S. agalactiae) and 67.86% (S. iniae), which were both higher than those of rSip groups,31.58% (S. agalactiae) and 35.71% (S. iniae), respectively. Our study indicated that BNC-rSip can induce protective immunity for tilapia through immersion immunization and may be an ideal candidate vaccine for controlling tilapia streptococcal disease. Full article

Subunit or inactivated vaccines comprise the majority of vaccines used against viral and bacterial pathogens. However, compared to their live/attenuated counterparts, these vaccines often demonstrate reduced immunogenicity, requiring multiple boosters and or adjuvants to elicit protective immune responses. For this reason, studies of adjuvants and the mechanism through which they can improve inactivated vaccine responses are critical for the development of vaccines with increased efficacy. Studies have shown that the direct conjugation of adjuvant to antigen promotes vaccine immunogenicity, with the advantage of both the adjuvant and antigen targeting the same cell. Using this strategy of direct linkage, we developed an inactivated influenza A (IAV) vaccine that is directly conjugated with the Toll-like receptor 7/8 agonist resiquimod (R848) through a heterobifunctional crosslinker. Previously, we showed that this vaccine resulted in improved protection and viral clearance in newborn nonhuman primates compared to a non-adjuvanted vaccine. We subsequently discovered that the choice of linker used to conjugate R848 to the virus alters the stimulatory activity of the vaccine, promoting increased maturation and proinflammatory cytokine production from DC differentiated in vitro. With this knowledge, we explored how the choice of crosslinker impacts the stimulatory activity of these vaccines. We found that the linker choice alters signaling through the NF-κB pathway in human monocyte-derived dendritic cells (moDCs). Further, we extended our analyses to in vivo differentiated APC present in human peripheral blood, replicating the linker-dependent differences found in in vitro differentiated cells. Finally, we demonstrated in a mouse model that the choice of linker impacts the amount of IAV-specific IgG antibody produced in response to vaccination. These data enhance our understanding of conjugation approaches for improving vaccine immunogenicity. Full article

Understanding the risk factors associated with COVID-19 infection among healthcare workers is crucial for infection prevention and control. The aim of this study was to examine the risk of testing positive for COVID-19 among a multicenter cohort of workers, taking into account their occupational roles (medical professionals, staff in operational and administrative roles, or laboratory personnel) in healthcare settings. The data analyzed in this study included 2163 individuals with suggestive COVID-19 symptoms who underwent laboratory testing. The incidence rate in the study sample was calculated to be 15.3 cases per 10,000 person-days. The results from the multiple regression model indicated that job roles were not significantly associated with the risk of testing positive. However, age and the duration of the pandemic were identified as significant risk factors, with increasing age and longer pandemic duration being associated with a higher risk of testing positive. Additionally, vaccination was found to reduce the risk of testing positive. These findings provide valuable insights into COVID-19 transmission among indoor healthcare workers, highlighting the influence of age, pandemic duration, and vaccination on infection risk. Further research is needed to develop evidence-based strategies aimed at protecting healthcare workers and preventing virus spread in healthcare settings. Full article

COVID-19 caused significant morbidity and mortality amongst ethnic minority groups, but vaccine uptake remained lower than non-minoritised groups. Interventions to increase vaccine uptake among ethnic minority communities are crucial. This systematic review synthesises and evaluates behaviour change techniques (BCTs) in interventions to increase vaccination uptake in ethnic minority populations. We searched five databases and grey literature sources. From 7637 records identified, 23 studies were included in the review. Interventions were categorised using the Behaviour Change Wheel (BCW) and Behaviour Change Taxonomy v1. Vaccines included influenza, pertussis, tetanus, diphtheria, meningitis and hepatitis. Interventions were primarily delivered in health centres/clinics and community settings. Six BCW intervention functions and policy categories and 26 BCTs were identified. The main intervention functions used were education, persuasion and enablement. Overall, effective interventions had multi-components and were tailored to specific populations. No strong evidence was observed to recommend specific interventions, but raising awareness and involvement of community organisations was associated with positive effects. Several strategies are used to increase vaccine uptake among ethnic minority communities; however, these do not address all issues related to low vaccine acceptance. There is a strong need for an increased understanding of addressing vaccine hesitancy among ethnic minority groups. Full article

Aim: The objective of this study was to explore the potential correlation between COVID-19 infection or vaccination and levels of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. Methods: Among 6050 healthcare workers at the Ege University Hospital, a cohort study with 162 participants divided into three arms with 54 participants each was conducted. The three groups were selected as follows: those diagnosed with COVID-19 and not vaccinated (group 1), those diagnosed with COVID-19 and subsequently vaccinated with CoronaVac (group 2), and those not diagnosed with COVID-19 but vaccinated with two doses of CoronaVac (group 3). Antibody levels measured at the sixth month of follow-up were defined as the primary outcome. Results: At the sixth month, all serum samples tested positive for anti-S. Anti-S levels were found to be significantly higher in group 2 than in the other groups (p < 0.001). There were no differences in antibody levels between groups 1 and 3 (p = 0.080). Average antibody levels were found to be lower in office workers and males. Anti-N antibodies were found to be positive in 85.1% of subjects at the sixth month. In group 2, anti-N antibodies were detected in all samples at the sixth month. Anti-N antibody levels were not significantly different between groups 1 and 2 (p = 0.165). Groups 1 and 2 had significantly higher antibody levels than group 3 (p < 0.001). Conclusions: Vaccination or infection provide protection for at least 6 months. Those who have previously been diagnosed with COVID-19 do not need to be vaccinated in the early period before their antibody levels decrease. Full article

The COVID-19 mRNA vaccine is the first mRNA vaccine approved for human administration by both the U.S. Food and Drug Administration and the European Medicines Agency. Studies have shown that the immune response and the decay of immunity after vaccination with the COVID-19 vaccines are variable within a population. Host genetic factors probably contribute to this variability. In this study, we investigated the effect of the single-nucleotide polymorphisms rs12252 and rs34481144 in the interferon-induced transmembrane protein (IFITM) 3 gene on the humoral immune response after vaccination against COVID-19 with mRNA vaccines. Blood samples were collected from 1893 healthcare workers and medical students at multiple time points post-vaccination and antibody titers against the SARS-CoV-2 S1 protein receptor binding domain were determined at all time points. All participants were genotyped for the rs34481144 and rs12252 polymorphisms in the IFITM3 gene. After the second and third vaccinations, antibody titer levels increased at one month and decreased at six months (p < 0.0001) and were higher after the booster vaccination than after the basic immunization (p < 0.0001). Participants vaccinated with mRNA-1273 had a higher humoral immune response than participants vaccinated with BNT162b2. rs12252 had no effect on the antibody response. In contrast, carriers of the GG genotype in rs34481144 vaccinated with BNT162b2 had a lower humoral immune response compared to A allele carriers, which reached statistical significance on the day of the second vaccination (p = 0.03) and one month after the second vaccination (p = 0.04). Further studies on the influence of rs12252 and rs34481144 on the humoral immune response after vaccination against COVID-19 are needed. Full article

Background: Measles infection in the hospital setting is a major issue. Despite the availability of an effective vaccine, measles outbreaks continue to occur in some European countries. We aimed to evaluate the immunological status of medical students attending the Tor Vergata Polyclinic (PTV). Methods: Measles antibodies titers were assessed by venipuncture on a sample of 2717 medical students who underwent annual health surveillance visits from January 2021 to March 2023. Subjects showing serum IgG values above 1.0 S/CO were considered serologically protected. Personal data, country of origin, and main demographic characteristic were also collected. Results: 66.7% (1467 Italian and 346 foreign) of medical students showed protective IgG antibodies levels. Female students were serologically immune more frequently than males (68.6% vs. 63.3%; p < 0.01 at Chi2). The mean antibody titer was 1.72 S/CO, significantly higher in females than males (1.67 vs. 1.75, respectively; p < 0.05), and significantly related to age (p < 0.01). Albanian students, who were the largest foreign population in our study, showed a low serological protection rate (40/90: 44.4%). Conclusions: The proportion of serologically non-immune students is high, raising concerns about the possible risk of hospital transmission. Substantial differences in the rate of immunity have been found between subjects coming from different parts of Europe and the world. Pre-training assessment of all medical students and vaccination of susceptible individuals is highly recommended, particularly for those from low immunization rate countries. Full article

Novel lyssaviruses, the causative agents of rabies, continue to be described mostly due to increased surveillance in bat hosts. Biologicals for the prevention of rabies in humans have, however, remained largely unchanged for decades. This study aimed to determine if commercial rabies immunoglobulin (RIG) could neutralize diverse lyssaviruses. Two commercial preparations, of human or equine origin, were evaluated against a panel consisting of 13 lyssavirus species. Reduced neutralization was observed for the majority of lyssaviruses compared to rabies virus and was more evident for lyssaviruses outside of phylogroup I. Neutralization of more diverse lyssaviruses only occurred at very high doses, except for Ikoma lyssavirus, which could not be neutralized by the RIG evaluated in this study. The use of RIG is a crucial component of rabies post-exposure prophylaxis and the data generated here indicate that RIG, in its current form, will not protect against all lyssaviruses. In addition, higher doses of RIG may be required for neutralization as the genetic distance from vaccine strains increases. Given the limitations of current RIG preparations, alternative passive immunization options should be investigated. Full article

The advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular laboratories, is costly, and is difficult to adapt to the rapidly growing number of cancer patients. To provide a simpler but effective immune therapy, a whole-cell tumor vaccine protocol was established based on ultraviolet C (UCV)-irradiated 4T1 triple-negative breast cancer cells. The apoptosis of tumor cells after UVC irradiation was verified using resazurin and Annexin V/propidium iodide flow cytometric assays. Protective immunity was achieved in immunized BALB/c mice, showing partial remission. Adoptive transfer of splenocytes or plasma from the mice in remission showed a protective effect in the naive BALB/c mice that received a living 4T1 tumor cell injection. 4T1-specific IgG antibodies were recorded in the plasma of the mice following immunization with the whole-cell vaccine. Interleukin-2 (IL-2) and oligonucleotide 2006 (ODN2006) adjuvants were used for the transfer of splenocytes from C57BL/6 mice into cyclophosphamide-treated BALB/c mice, resulting in prolonged survival, reduced tumor growth, and remission in 33% of the cases, without the development of the graft-versus-host disease. Our approach offers a simple, cost-effective whole-cell vaccine protocol that can be administered to immunocompetent healthy organisms. The plasma or the adoptive transfer of HLA-matching immunized donor-derived leukocytes could be used as an immune cell therapy for cancer patients. Full article

In Italy, a sequential pneumococcal vaccination with conjugate vaccine (PCV) and polysaccharide vaccine (PPSV23) is recommended for individuals aged ≥ 65 years and those at risk for pneumococcal disease (PD) aged ≥ 6 years. The aim of this study was to assess the cost-effectiveness of the new vaccines, i.e., approved 15-valent and 20-valent PCVs. A published Markov model was adapted to evaluate the lifetime cost-effectiveness of vaccination with PCV15 + PPSV23 versus PCV13 + PPSV23, PCV20 alone, PCV20 + PPSV23, and No Vaccination. Simulated cohorts representing the Italian population, including individuals aged ≥ 65 years, those at risk aged 50–100 years, and those deemed high risk aged 18–100 years were assessed. Outcomes were accrued in terms of incremental PD cases, costs, quality-adjusted life years, life years, and the cost–utility ratio relative to PCV13 + PPSV23. The conservative base case analysis, including vaccine efficacy based on PCV13 data, showed that sequential vaccination with PCV15 or PCV20 in combination with PPSV23 is preferred over sequential vaccination with PCV13 + PPSV23. Especially in the high-risk group, PCV15 + PPSV23 sequential vaccination was dominant over No Vaccination and resulted in an ICUR of €3605 per QALY gained. Including PCV20 + PPSV23 into the comparison resulted in the domination of the PCV15 + PPSV23 and No Vaccination strategies. Additionally, explorative analysis, including the geometric mean titer (GMT) informed vaccine effectiveness (VE) was performed. In the low-risk and high-risk groups, the results of the GMT scenarios showed PCV15 + PPSV23 to be dominant over the other sequential vaccines. These findings suggest that if real-world studies would confirm a difference in vaccine effectiveness of PCV15 and PCV20 versus PCV13 based on GMT ratios, PCV15 + PPSV23 could prove a highly immunogenic and effective vaccination regime for the Italian adult population. Full article

Background: The longitudinal response to the COVID-19 vaccines among patients on hemodialysis with and without prior SARS-CoV-2 infection has not been well characterized. Methods: To guide vaccination strategies in patients on hemodialysis, it is critical to characterize the longevity and efficacy of the vaccine; therefore, we conducted a prospective single-center monthly antibody surveillance study between March 2021 and March 2022 to investigate the dynamic humoral response to a series of COVID-19 mRNA vaccines in patients on hemodialysis with and without prior SARS-CoV-2 infection. Monthly quantitative antibody testing was performed using the Beckman Coulter Access SARS-CoV-2 IgG Antibody Test©, which detects IgG antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Results: This cohort of 30 participants (mean age: 61 ± 3 years) predominantly self-identified as African American (97%) and male (53%). Eight participants (27%) had recovered from COVID-19 (recovered) before the vaccine initiation. All participants received two vaccine doses, and 86.6% received a 6-month booster dose. Among patients naïve to COVID-19, the antibody positivity rate (APR) was 55% post-first-dose, 91% post-second-dose, 50% pre-booster at 6 months, 100% post-booster, and 89% at 6 months post-booster. Recovered patients sustained a consistent 100% APR throughout the year. The naïve patients demonstrated lower peak antibody levels post-second-dose than the recovered patients (17.9 ± 3.2 vs. 44.7 ± 5.6, p < 0.001). The peak antibody levels post-booster showed no significant difference between both groups (27.1 ± 3.9 vs. 37.9 ± 8.2, p = 0.20). Two naïve patients contracted COVID-19 during the follow-up period. Conclusions: The patients naïve to COVID-19 exhibited an attenuated and foreshortened antibody response following two doses of the mRNA vaccines compared with the recovered patients, who maintained 100% APR before the booster dose. The 6-month booster dose counteracted declining immunity and stimulated antibody responses in the naïve patients, even in previously non-responsive patients. This observation implies that different booster vaccination strategies might be required for COVID-19-naïve and -recovered patients. Post-vaccination antibody testing may serve as a valuable tool for guiding vaccination strategies. Full article

The idea of a common mucosal immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway has been poorly understood. The consequent failure of the current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection, and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and cannot be achieved by systemic and mucosal vaccination for the prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome is demonstrated through a review of randomised controlled trials (RCTs) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced. This review is dedicated to two giants of mucosal immunology: Professors John Bienenstock and Allan Cripps. Their recent deaths are keenly felt by their colleagues and students. Full article

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future. Full article

Pregnant women are at higher risk of developing severe COVID-19 symptoms. Therefore, booster dose against COVID-19 was recommended for this special population in Jordan. However, vaccine hesitancy/refusal remains the main obstacle to providing immunity against the spread of COVID-19. Thus, the aim of this study is to examine the intention of pregnant/planning to get pregnant and lactating women towards receiving a booster dose against COVID-19 and its associated factors. A questionnaire was given to Jordanian pregnant/planning to get pregnant and lactating females. A total of 695 females were enrolled in the study. Older age, having a chronic disease, high education, high income, and high perceived risk of COVID-19 were significantly associated with higher knowledge about COVID-19. High perceived risk of COVID-19 was significantly associated with better practice. Participants who anticipated they might contract COVID-19 in the next six months, had high perceived risk of COVID-19, had high knowledge, had received the COVID-19 vaccine based on conviction, and smokers had higher intention to receive a booster dose of the COVID-19 vaccination. In order to increase pregnant and lactating women’s intention to receive a booster dose of the COVID-19 vaccine, public health organizations should consider developing comprehensive health education campaigns. Full article

Pregnant women are a highly vaccine-resistant population and face unique circumstances that complicate vaccine decision-making. Pregnant women are also at increased risk of adverse maternal and neonatal outcomes to many vaccine-preventable diseases. Several models have been proposed to describe factors informing vaccine hesitancy and acceptance. However, none of these existing models are applicable to the complex decision-making involved with vaccine acceptance during pregnancy. We propose a model for vaccine decision-making in pregnancy that incorporates the following key factors: (1) perceived information sufficiency regarding vaccination risks during pregnancy, (2) harm avoidance to protect the fetus, (3) relationship with a healthcare provider, (4) perceived benefits of vaccination, and (5) perceived disease susceptibility and severity during pregnancy. In addition to these factors, the availability of research on vaccine safety during pregnancy, social determinants of health, structural barriers to vaccine access, prior vaccine acceptance, and trust in the healthcare system play roles in decision-making. As a final step, the pregnant individual must balance the risks and benefits of vaccination for themselves and their fetus, which adds greater complexity to the decision. Our model represents a first step in synthesizing factors informing vaccine decision-making by pregnant women, who represent a highly vaccine-resistant population and who are also at high risk for adverse outcomes for many infectious diseases. Full article