Nowadays, mumps is re-emerging in highly vaccinated populations. Waning of vaccine-induced immunity plays a role, but antigenic differences between vaccine and mumps outbreak strains could also contribute to reduced vaccine effectiveness. CD8⁺ T cells play a critical role in immunity to viruses. However, limited data are available about sequence variability in CD8⁺ T cell epitope regions of mumps virus (MuV) proteins. Recently, the first set of naturally presented human leukocyte antigen Class I (HLA-I) epitopes of MuV was identified by us. In the present study, sequences of 40 CD8⁺ T cell epitope candidates, including previously and newly identified, obtained from Jeryl–Lynn mumps vaccine strains were compared with genomes from 462 circulating MuV strains. In 31 epitope candidates (78%) amino acid differences were detected, and in 17 (43%) of the epitope candidates the corresponding sequences in wild-type strains had reduced predicted HLA-I-binding compared to the vaccine strains. These findings suggest that vaccinated persons may have reduced T cell immunity to circulating mumps viruses due to antigenic differences. Full article

A universal influenza candidate vaccine that targets multiple conserved influenza virus epitopes from hemagglutinin (HA), neuraminidase (NA) and matrix (M2e) proteins was combined with the potent Army liposomal adjuvant (ALFQ) to promote induction of broad immunity to seasonal and pandemic influenza strains. The unconjugated and CRM-conjugated composite peptides formulated with ALFQ were highly immunogenic and induced both humoral and cellular immune responses in mice. Broadly reactive serum antibodies were induced across various IgG isotypes. Mice immunized with the unconjugated composite peptide developed antibody responses earlier than mice immunized with conjugated peptides, and the IgG antibodies were broadly reactive and neutralizing across Groups 1 and 2 influenza viruses. Multi-epitope unconjugated influenza composite peptides formulated with ALFQ provide a novel strategy for the development of a universal influenza vaccine. These synthetic peptide vaccines avoid the pitfalls of egg-produced influenza vaccines and production can be scaled up rapidly and economically. Full article

Four months into the SARS-CoV-2 vaccination campaign, only 10.7% of the Lebanese population have received at least one dose, raising serious concerns over the speed of vaccine roll-out and its impact in the event of a future surge. Using mathematical modeling, we assessed the short-term impact of various vaccine roll-out scenarios on SARS-CoV-2 epidemic course in Lebanon. At current population immunity levels, estimated by the model at 40% on 15 April 2021, a large epidemic wave is predicted if all social distancing restrictions are gradually eased and variants of concern are introduced. Reaching 80% vaccine coverage by the end of 2021 will flatten the epidemic curve and will result in a 37% and 34% decrease in the peak daily numbers of severe/critical disease cases and deaths, respectively; while reaching intermediate coverage of 40% will result in only a 10–11% decrease in each. Reaching 80% vaccine coverage by August would prevent twice as many severe/critical disease cases and deaths than if it were reached by December. Easing restrictions over a longer duration resulted in more favorable vaccination impact. In conclusion, for vaccination to have impact in the short-term, scale-up has to be rapid and reach high coverage (at least 70%), while sustaining social distancing measures during roll-out. At current vaccination pace, this is unlikely to be achieved. Concerted efforts need to be made to overcome local challenges and substantially scale up vaccination to avoid a surge that the country, with its multiple crises and limited health-care capacity, is largely unprepared for. Full article

Vaccination is one of the most effective ways to stop the spread of COVID-19. Understanding factors associated with intention to receive COVID-19 vaccines is the key to a successful vaccination programme. This cross-sectional study explored the rate of vaccination intention and identified its predictors using the health belief model (HBM) in the general population in Hong Kong during the pandemic. Data were collected between December 2020 and January 2021 via telephone surveys. Hierarchical logistic regression analysis was used to identify factors associated with intention to receive COVID-19 vaccines. A total of 1255 adults (>18 years, 53% female) completed the telephone survey. Overall, 42% indicated an intention to vaccinate, 31.5% showed vaccine hesitancy, and 26.5% reported refusal to receive any COVID-19 vaccines. Individuals who were men, older in age, working, with past experiences of other pandemics, less concerned with the vaccine safety, with poorer knowledge about COVID-19, and having greater levels of perceived susceptibility, self-efficacy, cues to action, and acceptance of governmental preventive measures related to COVID-19 were significantly more likely to report an intention to vaccinate. The low intention among the Hong Kong population reflects the importance of developing effective vaccination promotion campaigns with the predictors identified in this study. Full article

Understanding the potential impact of COVID-19 on receiving influenza vaccination among healthcare workers (HCWs) is of utmost importance. The purposes of the present cross-sectional study were to describe the characteristics and to explore the predictors of receiving influenza vaccination among a large cohort of Italian HCWs in hospital settings. Information was collected through an anonymous questionnaire from December 2020 through January 2021. General and practice characteristics, perceived risk of seasonal influenza, attitudes towards efficacy and safety of influenza vaccination, and reasons behind the decision to be vaccinated against influenza were explored. Fewer than half (46.2%) of HCWs agreed that influenza is a serious illness and perceived the risk of getting infected with influenza, and concerns about the safety of the vaccination were significant positive predictors. Fewer than half of the respondents were not concerned at all about the efficacy (48.6%) and safety (49.8%) of influenza vaccination, and 51.9% reported that they have not received a seasonal influenza vaccine during the previous season. The most mentioned reason for receiving the influenza vaccine in the current season was that influenza and COVID-19 share some similar symptoms. Study results will aid policymakers in developing vaccination education programs, promotion of trust to address negative misconceptions, and to achieve future high coverage among this high-risk group. Full article

Therapeutic vaccines based on dendritic cells offer a good approach to HIV-specific T-cell responses and partial control of the viral load after antiretroviral therapy interruption. The aim of the present study was to identify mRNA expression profiles and to assess the impact of the gut microbiome composition for predicting the viral load control after antiretroviral therapy interruption. We enrolled 29 patients to receive either placebo or a monocyte-derived dendritic cell vaccine. Patients with a decrease in their viral load of >0.5 log₁₀ copies/mL by 12 weeks after antiretroviral therapy interruption were considered responders. In total, 66 genes were considered differentially expressed between responders and non-responders. Enrichment analysis revealed several upregulated pathways involved in the host defense response to a virus via the type I interferon signaling pathway. Regarding the gut microbiota, responders showed enriched levels of Bacteroidetes (p < 0.005) and Verrucomicrobia (p = 0.017), while non-responders were enriched with Tenericutes (p = 0.049) and Actinobacteria (p < 0.005). We also found important differences at the genus level. However, we did not discover any effect of the dendritic cell vaccine on the transcriptome or the gut microbiota. An alternative analysis did characterize that the microbiota from responders were associated with the metabolic production of short-chain fatty acids, which are key metabolites in the regulation of intestinal homeostasis. The evidence now consistently shows that short-chain fatty acid depletion occurs in HIV-infected individuals receiving antiretroviral treatment. Full article

Background: COVID-19 vaccines have had expedited reviews without sufficient safety data. We wanted to compare risks and benefits. Method: We calculated the number needed to vaccinate (NNTV) from a large Israeli field study to prevent one death. We accessed the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register (lareb.nl) to extract the number of cases reporting severe side effects and the number of cases with fatal side effects. Result: The NNTV is between 200–700 to prevent one case of COVID-19 for the mRNA vaccine marketed by Pfizer, while the NNTV to prevent one death is between 9000 and 50,000 (95% confidence interval), with 16,000 as a point estimate. The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination. Conclusions: This lack of clear benefit should cause governments to rethink their vaccination policy. Full article

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo. Full article

Despite South Africa’s substantial investments in and efforts at ensuring universal access to immunisation services, progress has stalled and remains suboptimal across provinces and districts. An additional challenge is posed by the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has disrupted immunisation services globally, including in South Africa. While there is growing evidence that missed opportunities for vaccination (MOV) are a major contributor to suboptimal immunisation progress globally, not much is known about the burden and determinants of MOV in the South African context. Herein, we make a case for assessing MOV as a strategy to address current immunisation coverage gaps while mitigating the adverse impacts of the COVID-19 pandemic on immunisation services. We illustrate a practical implementation research approach to assessing the burden of MOV among children in primary care settings; for understanding the factors associated with MOV; and for designing, implementing, and evaluating context-appropriate quality improvement interventions for addressing missed opportunities. Such efforts are vital for building health system resilience and maintaining immunisation programme capacity to optimally deliver essential health services such as routine childhood immunisation, even during pandemics. Full article

Bats have been increasingly gaining attention as potential reservoir hosts of some of the most virulent viruses known. Numerous review articles summarize bats as potential reservoir hosts of human-pathogenic zoonotic viruses. For European bats, just one review article is available that we published in 2014. The present review provides an update on the earlier article and summarizes the most important viruses found in European bats and their possible implications for Public Health. We identify the research gaps and recommend monitoring of these viruses. Full article

Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized. Full article

To control circulating vaccine-derived type 2 poliovirus outbreaks, a more genetically stable novel Oral Poliovirus Vaccine type 2 (nOPV2) was developed by targeted modifications of Sabin 2 genome. Since the use of OPV2 made of Sabin 2 strain has been stopped, it is important to exclude the possibility that batches of nOPV2 are contaminated with Sabin 2 virus. Here, we report the development of a simple quantitative one-step reverse-transcription polymerase chain reaction assay for the detection and quantitation of Sabin 2 virus in the presence of overwhelming amounts of nOPV2 strain. The method is specific and linear within 8 log₁₀ range even in the presence of relevant amounts of nOPV2 virus. It is sensitive, with a lower limit of detection of 0.2 CCID₅₀/mL (an equivalent of 198 genome copies per mL), and generates reproducible results. This assay can be used for quality control and lot release of the nOPV2. Full article

Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Although most HPV infections are transient and asymptomatic, persistent infection with high-risk HPV types may results in diseases. Although there are currently three effective and safe prophylactic HPV vaccines that are used across the world, HPV vaccination coverage remains low. This review evaluates the effects of the interventions to improve HPV vaccination coverage. We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Scopus, and the World Health Organization International Clinical Trials Registry Platform and checked the reference lists of relevant articles for eligible studies. Thirty-five studies met inclusion criteria. Our review found that various evaluated interventions have improved HPV vaccination coverage, including narrative education, outreach plus reminders, reminders, financial incentives plus reminders, brief motivational behavioral interventions, provider prompts, training, training plus assessment and feedback, consultation, funding, and multicomponent interventions. However, the evaluation of these intervention was conducted in high-income countries, mainly the United States of America. There is, therefore, a need for studies to evaluate the effect of these interventions in low-and middle-income countries, where there is a high burden of HPV and limited HPV vaccination programs. Full article

The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology. Full article

Background: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). Methods: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. Results: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47–56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). Conclusions: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results. Full article