Effective Vaccine Research Articles

Immunogenicity of intraperitoneal and intranasal liposome adjuvanted VLP vaccines against SARS-CoV-2 infection

Humans get SARS-CoV-2 infection mainly through inhalation; thus, vaccine that induces protective immunity at the virus entry site is important for early control of the infection. In this study, two anionic liposome (L)-adjuvanted VLP vaccines against SARS-CoV-2 were formulated. Baculovirus-Sf21 insect cell system was used for production of VLPs made of full-length S, M and E proteins. S protein of one vaccine (L-SME-VLPs) contained furin cleavage site at the S1/S2 junction, while that of another vaccine (L-S′ME-VLPs) did not. Both vaccines were innocuous and immunogenic when administered IP and IN to mice. Mice immunized IP with L-SME-VLPs/L-S′ME-VLPs (three doses, two-weeks intervals) had serum virus neutralizing (VN) antibodies (in falling order of isotype frequency): IgG3, IgA and IgG2a/IgG3, IgA and IgM, respectively. The L-S′ME VLPs vaccine induced significantly higher serum VN antibody titers than the L-SME-VLPs vaccine. All mice immunized IN with both vaccines had significant rise of VN antibodies in their bronchoalveolar lavage fluids (BALF). The VN antibodies in 67% of immunized mice were Th1- isotypes (IgG2a and/or IgG2b); the immunized mice had also other antibody isotypes in BALF. The intranasal L-S′ME-VLPs should be tested further step-by-step towards the clinical use as effective and safe vaccine against SARS-CoV-2.

Characterization of T and B cell epitopes in PvCyRPA by studying the naturally acquired immune response in Brazilian Amazon communities

Plasmodium vivax, a challenging species to eliminate, causes millions of malaria cases globally annually. Developing an effective vaccine is crucial in the fight against vivax malaria, but considering the limited number of studies focusing on the identification and development of P. vivax-specific vaccine candidates, exploring new antigens is an urgent need. The merozoite protein CyRPA is essential for P. falciparum growth and erythrocyte invasion and corresponds to a promising candidate antigen. In P. vivax, a single study with multiple vaccine candidates indicates PvCyRPA with strong association with protection, outperforming classic malaria vaccine candidates. However, little is known about the specific naturally acquired response in the Americas, as well as the antigen epitope mapping. For this reason, we aimed to investigate the cellular and humoral immune response elicited against PvCyRPA in Brazilian endemic areas to identify the existence of immunodominant regions and the potential of this protein as a single or even a multi-stage specific malaria vaccine candidate for P. vivax. The results demonstrated that PvCyRPA is naturally immunogenic in Brazilian Amazon individuals previously exposed to malaria, which presented anti-PvCyRPA cytophilic antibodies. Moreover, our data show that the protein also possesses important immunogenic regions with an overlap of B and T cell epitopes. These data reinforce the possibility of including PvCyRPA in vaccine formulations for P. vivax.

Genomic characteristics, disease outcome and heterologous vaccine effectiveness among cases with SARS CoV-2 infection

BackgroundIn the pursuit of global health security, continuous monitoring of vaccine effectiveness across various viral strains emerges as a crucial imperative. The emergence of SARS-CoV-2 major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron, has added complexity to the COVID-19 vaccination landscape.ObjectivesTo assess illness severity, evaluate vaccine efficacy across varying doses and types, and determine effectiveness against major VOCs within the population.MethodsThis retrospective cohort study, conducted in Abu Dhabi, United Arab Emirates, focuses on a cohort of 44,073 SARS-CoV-2 positive cases from February 2021 to May 2022, dominated by the Delta and Omicron variants. The study employed a nested case-control design, analyzing hospital admissions for confirmed SARS-CoV-2 infection.ResultsVaccine effectiveness was higher among heterologus-boosted individuals at 87% (95% CI:79%-93%) compared to homologus-boosted individuals at 59% (95% CI: 48%-68%) and fully vaccinated, non-boosted adults at 53% (95% CI: 46%-59%). These findings highlight the importance of heterologous boosting, particularly against rapidly evolving viral variants, offering valuable insights for refining pandemic response strategies.ConclusionThe study underscores the critical need for ongoing assessment and adaptation of vaccination strategies to the evolving viral landscape.

Multi-strain modeling of influenza vaccine effectiveness in older adults and its dependence on antigenic distance

Influenza vaccine effectiveness (VE) varies seasonally due to host, virus and vaccine characteristics. To investigate how antigenic matching and dosage impact VE, we developed a mechanistic knowledge-based mathematical model. Immunization with a split vaccine is modeled for exposure to A/H1N1 or A/H3N2 virus strains. The model accounts for cross-reactivity of immune cells elicited during previous immunizations with new antigens. We simulated vaccine effectiveness (sVE) of high dose (HD) versus standard dose (SD) vaccines in the older population, from 2011 to 2022. We find that sVE is highly dependent on antigenic matching and that higher dosage improves immunogenicity, activation and memory formation of immune cells. In alignment with clinical observations, the HD vaccine performs better than the SD vaccine in all simulations, supporting the use of the HD vaccine in the older population. This model could be adapted to predict the impact of alternative virus strain selection on clinical outcomes in future influenza seasons.

Association of COVID-19 Vaccine Intake with Diagnosis, Hospitalization, and Oxygenation/Ventilation: A Longitudinal Analysis, 2021–2022, Japan

Background/Objectives: Japan’s COVID-19 vaccination campaign achieved high coverage by 2022, yet limited national-level data has hindered evaluations of vaccine effectiveness. This study analyzed the impact of vaccines on infection outcomes while considering socioeconomic and behavioral factors in the Japanese population. Methods: A total of 19,482 individuals aged 16–81 years, who participated in both the 2021 (baseline) and 2022 (follow-up) waves of an Internet-based survey, were analyzed. Vaccine intake during the follow-up period (0/1/2+ doses) served as the exposure, while outcomes included COVID-19 diagnosis, hospitalization, and receipt of oxygenation/ventilation. Adjusted prevalence ratios (APRs) were calculated using Poisson regression models, controlling for baseline characteristics such as vaccination status, infection history, underlying medical conditions, socioeconomic factors, and preventive behaviors. Results: Overall, 81.6% of respondents received at least 1 dose of COVID-19 vaccine during the follow-up period. Among those without COVID-19 history at baseline (N = 19,182), 10.9% were diagnosed with COVID-19 in the past year, and 6.6% in the past 2 months. Respondents who received 1 or 2+ doses had lower diagnosis rates (APR = 0.76 and 0.43, respectively). For the past 2 months, only those with 2+ doses showed a significant reduction (APR = 0.51). Among 1999 diagnosed cases, those with 1 or 2+ doses showed lower hospitalization and oxygenation/ventilation likelihoods, though these differences were not statistically significant. Conclusions: The results supported the protective effect of COVID-19 vaccines against infection. Continued research is essential to further clarify the complex influence of vaccination, individual characteristics, and preventive behaviors on COVID-19 morbidity at the population level.

Prevalence, Characteristics, and Distribution of Human Papillomavirus According to Age and HIV Status in Women of Eastern Cape Province, South Africa

Human papillomavirus (HPV) is a sexually transmitted infection associated with the development of cervical cancer. This study investigated cervical HPV prevalence, characteristics, and distribution according to age and human immunodeficiency virus (HIV) status among women attending a public community health facility in the Eastern Cape Province of South Africa. A total of 325 participants (aged 18 to 60) visiting a community health facility for any reason were recruited. Cervical HPV infection was detected using the Seegene Anyplex™ II HPV28 assay (Seegene Inc., Seoul, South Korea). Overall HPV prevalence was 65.2% (95% CI: 59.9–70.2%), with the highest prevalence of 80.9% (95% CI: 67.2–89.8%) observed in the 18–25-year-old age group and the lowest prevalence of 46.3% (95% CI: 35.8–57.1%) in the 46–60-year-old age group. HR-HPV infection was found to decrease with increasing age (p < 0.001) in the overall population and according to HIV status. In contrast, LR-HPV infection was found to significantly decrease with age among HIV-negative women (p = 0.001) but not for the overall population and HIV-positive women. A proportion of 12.9% were infected with one or more HPV types covered by the Cervarix® HPV vaccine (HPV-16 and/or -18), 18.8% (by those covered by Gardasil®4 (HPV-6, -11, -16 and/or -18), and 42.2% by those covered by Gardasil®9 (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58). The alpha-9 HPV species was the most dominant species (40.6%), followed by the alpha-7 species (29.8%). High overall HPV, HR-HPV, and alpha-9 species prevalence were observed among the women attending the public health facility. These findings contribute to the limited HPV distribution data among the Eastern Cape women, which could be used to improve HPV-related policy and assess the effectiveness of the HPV vaccination.

Efficacy of an Inactivated Whole‐Virus A/Victoria/361/2011 (IVR‐165) (H3N2) Influenza Vaccine in Ferrets

ABSTRACTIt has been reported that the high‐growth reassortant (HGR) A(H3N2) influenza viruses used for split influenza vaccine (SV) production have some amino acid substitutions in hemagglutinin due to egg adaptation during virus propagation, causing antigenic differences between HGR and epidemic viruses. To clarify whether inactivated whole‐virus vaccine (WV) derived from the A(H3N2) HGR virus possessing egg adaptation could induce cross‐protective immune responses against epidemic A(H3N2) viruses, the efficacy of WV was compared with that of SV in a ferret model. When the ferrets immunized with WV or SV derived from HGR A/Victoria/361/2011 (IVR‐165) virus were challenged with the homologous virus A/Victoria/361/2011 (IVR‐165) or its original cell‐propagated A/Victoria/361/2011 virus, respectively, WV successfully shortened the duration of virus shedding of both challenge viruses, whereas SV shortened only that of the homologous virus, A/Victoria/361/2011 (IVR‐165). When WV‐immunized ferrets were challenged with A/Fukushima/69/2015 virus, which is an epidemic virus antigenically different from the A/Victoria/361/2011 virus, WV could shorten the duration of shedding of this virus. In addition, we found that early induction of nasal IgG and IgA antibodies by vaccines helped shorten the virus‐shedding period, although this was dependent on the degree of difference in antigenicity of the challenge virus. These results indicate that vaccination with WV, not with SV, would be a solution to avoid decreased vaccine effectiveness due to the antigenic change of HGR virus by egg adaptation during virus propagation.

Examining the Effect of Parental COVID‐19 Vaccination Prior to Birth and the Association Between COVID‐19 and Cancer in Children Under Six

ABSTRACTIntroductionThe biology of COVID‐19 has intricate links to childhood cancer, exacerbated by pandemic disturbances. This research aims to explore the association between childhood cancer in children under 6 years old and COVID‐19 immunisation, in addition to the effects of vaccination on parents before delivery.MethodThe study employs a case‐control approach, gathering informed consent and matching factors like age, marital status, and socioeconomic status between cases and controls. A survey was distributed, culminating in 191 children under six, with data from 136 diagnosed cancer cases collected in 2023, adhering to methodological standards in epidemiological research. The analysis utilised SPSS28, employing chi‐square testing and logistic regression.ResultChi‐square testing confirmed a significant rise in childhood cancer rates post‐COVID‐19 pandemic compared to pre‐pandemic rates. Key factors influencing cancer incidence include the mother's age at childbirth, parental vaccination history before pregnancy, maternal vaccination details during pregnancy, the child's COVID‐19 infection status, and maternal marriage age. Notably, younger mothers faced higher COVID‐19 infection risks, but vaccination appears to mitigate paediatric cancer risk.ConclusionThe post‐pandemic surge in childhood cancer underscores a complex interplay of early exposures and maternal viral infections. Emphasising vaccination's protective effects before and during pregnancy, the study advocates integrating vaccination into maternal health programs. Public health measures should promote immunisation and address socioeconomic inequalities to lower paediatric cancer risk, aligning with previous studies linking parental health behaviours to childhood cancer incidence.

Investigating Osteomyelitis as a Rare Adverse Effect of Vaccination in the Pediatric Population

Investigating Osteomyelitis as a Rare Adverse Effect of Vaccination in the Pediatric Population

Recombinant characterization and pathogenicity of a novel L1C RFLP-1-4-4 variant of porcine reproductive and respiratory syndrome virus in China

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide and is caused by the PRRS virus (PRRSV), which has complex genetic variation due to frequent mutations, indels, and recombination. The emergence of PRRSV L1C.5 in 2020 in the United States has raised worldwide concerns about PRRSV with the RFLP 1-4-4 pattern and lineage 1C. However, studies on the pathogenic characteristics, epidemiological distribution, and effectiveness of vaccines against PRRSV with L1C and RFLP1-4-4 pattern in China are still insufficient. In this study, a novel recombinant variant of PRRSV with RFLP 1-4-4 and lineage 1C features, different from L1C.5 in the United States, was isolated in China in 2021. In pathogenicity experiments in specific pathogen-free piglets or farm piglets, 60–100% of artificially infected experimental piglets died with high fever and respiratory symptoms. Inflammatory cytokine and chemokine levels were upregulated in infected piglets. A commercially modified live vaccine against highly pathogenic PRRSV did not provide effective protection when the vaccinated piglets were challenged with the novel L1C-1-4-4 variant. Therefore, this strain merits special attention when devising control and vaccine strategies. These findings suggest that extensive joint surveillance is urgently needed and that vaccine strategies should be updated to prevent the disease from spreading further.

Canine Brucellosis: A Comprehensive Review

Canine brucellosis, caused by Brucella canis, is a global infectious and zoonotic disease that poses a significant public health risk due to the close interactions between dogs and humans. In dogs, the disease can lead to abortion outbreaks, reproductive failures, lymphadenopathy, and occasionally osteoarticular issues. Asymptomatic infections are also relatively common. In humans, brucellosis typically presents with a febrile illness and non-specific symptoms such as splenomegaly, fatigue, and weakness. The disease is notably problematic in breeding programs due to reproductive failures, including infertility and abortion, leading to substantial economic losses. Transmission occurs through direct contact with infected bodily fluids, particularly during mating, or via contaminated environments. Diagnosing canine brucellosis accurately is critical and can be achieved using various methods, including bacterial cultures, serological tests like the Rose Bengal Plate Test (RBPT) and Enzyme-Linked Immunosorbent Assay (ELISA), and molecular techniques such as polymerase chain reaction (PCR). Treatment is limited, with neutering and antibiotic therapy being the main approaches, though these do not always ensure complete recovery. Preventive measures are essential and include regular screening of breeding dogs, isolation of infected animals, and strict biosecurity protocols. Given its zoonotic potential, it is crucial for veterinary professionals and pet owners to be aware of the disease. Increased awareness and future research on new diagnostic methods and effective vaccines are vital for improving control strategies and reducing the impact of canine brucellosis on both canine and human health.

Benchmark Investigation of SARS-CoV-2 Mutants’ Immune Escape with 2B04 Murine Antibody: A Step Towards Unraveling a Larger Picture

Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. Nonetheless, reinfection by newly emerging subvariants, particularly the latest JN.1 strain, remains common. The rapid mutation of this virus demands a fast response from the scientific community in case of an emergency. While the immune escape of earlier variants was extensively investigated, one still needs a comprehensive understanding of how specific mutations, especially in the newest subvariants, influence the antigenic escape of the pathogen. Here, we tested comprehensive in silico approaches to identify methods for fast and accurate prediction of antibody neutralization by various mutants. As a benchmark, we modeled the complexes of the murine antibody 2B04, which neutralizes infection by preventing the SARS-CoV-2 spike glycoprotein’s association with angiotensin-converting enzyme (ACE2). Complexes with the wild-type, B.1.1.7 Alpha, and B.1.427/429 Epsilon SARS-CoV-2 variants were used as positive controls, while complexes with the B.1.351 Beta, P.1 Gamma, B.1.617.2 Delta, B.1.617.1 Kappa, BA.1 Omicron, and the newest JN.1 Omicron variants were used as decoys. Three essentially different algorithms were employed: forced placement based on a template, followed by two steps of extended molecular dynamics simulations; protein–protein docking utilizing PIPER (an FFT-based method extended for use with pairwise interaction potentials); and the AlphaFold 3.0 model for complex structure prediction. Homology modeling was used to assess the 3D structure of the newly emerged JN.1 Omicron subvariant, whose crystallographic structure is not yet available in the Protein Database. After a careful comparison of these three approaches, we were able to identify the pros and cons of each method. Protein–protein docking yielded two false-positive results, while manual placement reinforced by molecular dynamics produced one false positive and one false negative. In contrast, AlphaFold resulted in only one doubtful result and a higher overall accuracy-to-time ratio. The reasons for inaccuracies and potential pitfalls of various approaches are carefully explained. In addition to a comparative analysis of methods, some mechanisms of immune escape are elucidated herein. This provides a critical foundation for improving the predictive accuracy of vaccine efficacy against new viral subvariants, introducing accurate methodologies, and pinpointing potential challenges.

FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment

ABSTRACT Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.

Beneficial Impact of Vaccination Against SARS-CoV-2 on the Mental Health of IPF Patients

Background: Depression and anxiety represent significant comorbidities in idiopathic pulmonary fibrosis (IPF) patients, affecting their quality of life. The COVID-19 pandemic has had an uneven impact on global mental health. The Hospital Anxiety and Depression Scale (HADS) constitutes a validated tool to identify anxiety disorders and depression. The aim of this multicentre study was to evaluate the effect of COVID-19 vaccination on depression and anxiety in IPF patients. Methods: Consecutive IPF patients (median 73.5 years) who are regularly followed-up with were included in the study. Demographics, functional, and clinical were recorded. The HADS score was calculated before and one month after vaccination against COVID-19 in all participants. A Wilcoxon signed ranks test was conducted. Results: A total of 180 IPF patients (median 73.5 years) were included in the study. Among them, 145 patients (81%) received antifibrotic treatment. A significant reduction in HADS, both in anxiety and depression scales, was observed one month after vaccination against SARS-COV-2), independent of age, smoking, lung function impairment, and prior history of depression (p < 0.01). Conclusions: A higher Hospital Anxiety and Depression Scale score was detected before vaccination against COVID-19. It seems that vaccination also offered a beneficial effect on depression and anxiety in IPF patients, independent of age, smoking, lung function impairment, and prior history of depression.

Mathematical analysis of a three-strain model for dengue with vaccination

Abstract Dengue has emerged as the most widespread mosquito-borne ailment in humans, causing an estimated 390 million infections within the endemic regions of the world annually. In this paper, a novel mathematical model is proposed for three strains of dengue virus with vaccination measures. Some of the important qualitative analysis carried out are as follows: The dengue serotypes 1, 2 and 3 sub-models are qualitatively analyzed, using well constructed candidates of Lyapunov function. The sub-models' infection-free equilibria are proven to be locally asymptotically stable.The infection-free and endemic equilibria of the sub-models are established to be globally asymptotically stable. The complete model's infection-free equilibrium is proven to be locally and globally asymptotically stable. Also, simulations are also presented to validate the theoretical analysis in the paper. The solution profiles of all epidemiological compartments when the reproduction numbers are both below one and greater than one are graphically presented. It was observed that, for the scenarios when the dengue reproduction number $\mathcal{R}_{0}$ is below and above one, the solution trajectories converge to the infection-free and dengue-endemic steady states, respectively. Sensitivity analyses using the Latin Hypercube Sampling (LHS), and also using contour plots and surface plots are performed on the dengue serotypes associated reproduction numbers. The impact of influential parameters are graphically presented. Worthy of mention, is the significant impact of dengue transmission rates (positively correlated) and dengue vaccination rates and vaccine effectiveness levels (negatively correlated). Different scenario analyses to investigate the impact of dengue vaccination measures are presented. It was observed that enhanced dengue vaccination programme under the administration of safe and highly effective vaccine could curtail the spread and co-circulation of different dengue serotypes within the population.

The Impact of the U.S. Maternal Tdap Vaccination Program on Preventing Pertussis in Infants 2-<6 Months of Age: A Case-control Evaluation

Abstract Background To protect infants aged <2 months against pertussis, the United States recommends Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during each pregnancy. Data are limited on the strategy’s effectiveness against pertussis in infants aged ≥2 months. Methods Pertussis cases aged 2-<6 months with cough onset between 1/1/2011-12/31/2014 were identified in six U.S. states. Controls were 2-<6 months of age, hospital-matched, and selected by birth certificate. Mothers were interviewed to collect demographic and healthcare information. Provider-verified vaccination history was obtained for infants and mothers. Adjusted odds ratios (aORs) were calculated using conditional logistic regression; overall vaccine effectiveness (VE) was estimated as (1 - aOR) x 100. To describe maternal Tdap VE modified by infant DTaP (diphtheria and tetanus toxoids, and acellular pertussis) doses, case-control sets were unmatched and a time-to-event analysis conducted through a Generalized Linear Mixed Model. Results A total of 335 cases and 927 controls were enrolled. The overall adjusted VE estimate for Tdap during pregnancy was 45.6% (95% confidence interval [CI], 5.8% – 68.5%) and increased slightly, but not significantly against infant hospitalization (55.7% (-116.8% – 90.9%)). Although point estimates were not significant, VE was modified by infant DTaP doses (58.8% (-6.0% – 84.0%) for zero DTaP doses, 30.5% (-21.4% – 60.2%) for one DTaP dose, and 3.2% (-170.8% – 65.4%) for two DTaP doses). Conclusions Our study suggests that there is some benefit of maternal Tdap vaccination beyond the first two months of life, however, on-time vaccination of infants remains critical to maintain protection from pertussis.

Prospective clinical surveillance for severe acute respiratory illness and COVID-19 vaccine effectiveness in Kenyan hospitals during the COVID-19 pandemic.

There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. We collected data on demographic and clinical characteristics, SARS-CoV-2 infection and COVID-19 vaccination status and, admission episode outcomes. We determined COVID-19 vaccine effectiveness (VE) against admission with SARS-CoV-2 positive severe acute respiratory illness (SARI) (i.e., COVID-19) andprogression to inpatient mortality among patients admitted with SARI, using a test-negative case control design. Of the 52,636 patients included in the study, 17,950 (34.1%) were admitted with SARI. The median age was 50 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, Human Immunodeficiency Virus (HIV) infection and Diabetes Mellitus were the most common chronic comorbidities. SARS-CoV-2 test results were positive in 2,364 (27.9%) of the 8,471 patients that underwent testing. After adjusting for age, sex and presence of a chronic comorbidity, SARI patients were more likely to progress to inpatient mortality compared to non-SARI patients regardless of their SARS-CoV-2 infection status (adjusted odds ratio (aOR) for SARI and SARS-CoV-2 negative patients 1.22, 95% CI 1.10-1.37; and aOR for SARI and SARS-CoV-2 positive patients 1.32, 95% CI 1.24-1.40). After adjusting for age, sex and presence of a chronic comorbidity, COVID-19 VE against progression to inpatient mortality following admission with SARI for those with a confirmed vaccination status was 0.59 (95% CI 0.27-0.77). We have provided a comprehensive description of the demographic and clinical pattern of admissions with SARI in Kenyan hospitals during the COVID-19 pandemic period as well as the COVID-19 VE for these patients. These data were useful in providing situational awareness during the first three years of the pandemic in Kenya and informing national response measures.

Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23 and beyond: protocol for a pragmatic sub-study

Introduction During the COVID-19 pandemic, extensive research was conducted on SARS-CoV-2; however, important questions about other respiratory pathogens remain unanswered. A severe influenza season in 2022–2023 with simultaneous circulation of SARS-CoV2 and respiratory syncytial virus is anticipated. This sub-study aims to determine the incidence and impact of these respiratory viruses on healthcare workers, the symptoms they experienced, the effectiveness of both COVID-19 and influenza vaccination and the burden of these infections on the National Health Service (NHS) workforce. Methods and analysis This is a longitudinal prospective cohort sub-study, utilising the population and infrastructure of the SARS-CoV-2 Immunity & Reinfection Evaluation (SIREN) study, which focuses on hospital staff in the UK. Participants undergo fortnightly nucleic acid amplification testing on a multiplex assay including SARS-CoV-2, influenza A and B and RSV, regardless of symptoms. Questionnaires are completed every two weeks, capturing symptoms, sick days, exposures, and vaccination records. Serum samples are collected monthly or quarterly from participants associated with a SIREN site. This sub-study commenced on 28/11/22 to align with the predicted influenza season and participants’ influenza vaccine status. The SIREN Participant Involvement Panel shaped the aims and methods for the study, highlighting its acceptability. UK devolved administrations were supported to develop local protocols. Analysis plans include incidence of asymptomatic and symptomatic infection, comparisons of vaccination coverage, assessment of sick day burden, and effectiveness of seasonal influenza against infection and time off work. Data are also integrated into UKHSA nosocomial modelling. Ethics and dissemination The protocol was approved by the Berkshire Research Ethics Committee (IRAS ID 284460, REC Reference 20SC0230) on 14/11/2022. Participants were informed in advance. As the frequency and method of sampling remained the same, implied consent processes were approved by the committee. Participants returning to the study give informed consent. Regular reports to advisory groups and peer-reviewed publications are planned to disseminate findings and inform decision making. Clinical trial registration number: ISRCTN11041050; registration date: 12 January 2021. Sub study included in protocol version: v8.0, and amended in v9.0

VP8 Mosaic Nanoparticles Elicit Cross-Neutralizing Immune Responses and Provide Protection Against Heterotypic Rotavirus Challenge in Mice.

Group A rotaviruses (RVA) remain one of the dominant pathogens causing diarrhea in children under 5 years of age worldwide, despite a sharp decrease of RVA-associated diarrhea and mortality since the introduction of rotavirus vaccines. The decreased effectiveness of live attenuated rotavirus vaccines, coupled with the emergence of new rotavirus genotypes and the risk of cross-species virus transmission, underscores the necessity to develop more effective and broad-spectrum rotavirus vaccines. In this study, we utilized nanoparticles coupled with the SpyCatcher-SpyTag system to effectively display the truncated VP8-1 protein. The modular display of the monovalent VP8-1 proteins markedly increased the immunogenicity of VP8-1. Furthermore, the bivalent display of VP8-1 proteins from simian rotavirus SA11 and lamb rotavirus LLR on the same particle not only increased immunogenicity against homotypic antigens but also elicited robust heterotypic immune responses and conferred effective protection against a distant heterotypic rotavirus with sequence identities of only 62%-66% in an adult mouse model. Therefore, mosaic VP8 nanoparticles could be considered as a viable strategy for the development of the next-generation broad-spectrum rotavirus vaccine.

An Immunoinformatic Approach for Identifying and Designing Conserved Multi-Epitope Vaccines for Coronaviruses

Background/Objectives: The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for three major viral outbreaks, and the likelihood of future outbreaks caused by these viruses is high and nearly inevitable. Therefore, effective prophylactic universal vaccines targeting multiple circulating and emerging coronavirus strains are warranted. Methods: This study utilized an immunoinformatic approach to identify evolutionarily conserved CD4+ (HTL) and CD8+ (CTL) T cells, and B-cell epitopes in the coronaviral spike (S) glycoprotein. Results: A total of 132 epitopes were identified, with the majority of them found to be conserved across the bat CoVs, pangolin CoVs, endemic coronaviruses, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Their peptide sequences were then aligned and assembled to identify the overlapping regions. Eventually, two major peptide assemblies were derived based on their promising immune-stimulating properties. Conclusions: In this light, they can serve as lead candidates for universal coronavirus vaccine development, particularly in the search for pan-coronavirus multi-epitope universal vaccines that can confer protection against current and novel coronaviruses.