Low Vaccine Efficacy Research Articles

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE.

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD-CD27- 'double-negative (DN)' DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.

A two-strain COVID-19 co-infection model with strain 1 vaccination

COVID-19 has caused substantial morbidity and mortality worldwide. Previous models of strain 1 vaccination with re-infection when vaccinated, as well as infection with strain 2 did not consider co-infected classes. To fill this gap, a two co-circulating COVID-19 strains model with strain 1 vaccination, and co-infected is formulated and theoretically analyzed. Sufficient conditions for the stability of the disease-free equilibrium and single-strain 1 and -strain 2 endemic equilibria are obtained. Results show as expected that (1) co-infected classes play a role in the transmission dynamics of the disease (2) a high efficacy vaccine could effectively help mitigate the spread of co-infection with both strain 1 and 2 compared to the low-efficacy vaccine. Sensitivity analysis reveals that the main drivers of the effective reproduction number Re are primarily the effective contact rate for strain 2 (β2), the strain 2 recovery rate (τ2), and the vaccine efficacy or infection reduction due to the vaccine (η). Thus, implementing intervention measures to mitigate the spread of COVID-19 should not ignore the co-infected individuals who can potentially spread both strains of the disease.

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

Immunogenicity, safety, and efficacy of a tetravalent dengue vaccine in children and adolescents: an analysis by age group.

Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4-5 years; 6-11 years; or 12-16 years). Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically-confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers; GMTs); and safety were evaluated per age group through ∼4 years post-vaccination. VE against VCD across serotypes was 43.5% (95% confidence interval: 25.3%, 57.3%) for 4-5 year-olds; 63.5% (56.9%, 69.1%) for 6-11 year-olds, and 67.7% (57.8%, 75.2%) for 12-16 year-olds. VE against hospitalized VCD was 63.8% (21.1%, 83.4%), 85.1% (77.1%, 90.3%), and 89.7% (77.9%, 95.2%), for the three age groups, respectively. GMTs remained elevated against all four serotypes for ∼4 years post-vaccination, with no evident differences across age groups. No clear differences in safety by age were identified. This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4-16 years of age living in dengue endemic areas. Relatively lower VE in 4-5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group.

Ex Pluribus Unum: The CD4 T Cell Response against Influenza A Virus.

Current Influenza A virus (IAV) vaccines, which primarily aim to generate neutralizing antibodies against the major surface proteins of specific IAV strains predicted to circulate during the annual 'flu' season, are suboptimal and are characterized by relatively low annual vaccine efficacy. One approach to improve protection is for vaccines to also target the priming of virus-specific T cells that can protect against IAV even in the absence of preexisting neutralizing antibodies. CD4 T cells represent a particularly attractive target as they help to promote responses by other innate and adaptive lymphocyte populations and can also directly mediate potent effector functions. Studies in murine models of IAV infection have been instrumental in moving this goal forward. Here, we will review these findings, focusing on distinct subsets of CD4 T cell effectors that have been shown to impact outcomes. This body of work suggests that a major challenge for next-generation vaccines will be to prime a CD4 T cell population with the same spectrum of functional diversity generated by IAV infection. This goal is encapsulated well by the motto 'ex pluribus unum': that an optimal CD4 T cell response comprises many individual specialized subsets responding together.

The role of vaccine status homophily in the COVID-19 pandemic: a cross-sectional survey with modelling

BackgroundVaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy.MethodsResidents of British Columbia, Canada, aged ≥ 16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy.ResultsVaccine homophily was observed among those with 0, 2, or 3 doses of the vaccine. Greater homophily was observed among those who had more doses of the vaccine (p < 0.0001). Those with fewer vaccine doses had larger contact networks (p < 0.0001), were more likely to report prior COVID-19 (p < 0.0001), and reported lower compliance with COVID-19 prevention guidelines (p < 0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Furthermore, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as to an elevated force of infection from unvaccinated to suboptimally vaccinated individuals under conditions of low vaccine efficacy.InterpretationThe uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis

BackgroundTo eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme.MethodsUsing three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021–2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme.ResultsOver the years 2021–2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1–130.4) and 146.8 million (114.1–161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6–169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14–3.82) USD in low-income countries to 44.83 (3.75–85.64) USD in high-income countries, assuming one dose confers 30-year protection.ConclusionsResults were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

Comparison of SARS-Cov-2 omicron variant with the previously identified SARS-Cov-2 variants in Egypt, 2020-2022: insight into SARS-Cov-2 genome evolution and its impact on epidemiology, clinical picture, disease severity, and mortality.

The o severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has killed millions of people and caused widespread concern around the world. Multiple genetic variants of SARS-CoV-2 have been identified as the pandemic continues. Concerns have been raised about high transmissibility and lower vaccine efficacy against omicron. There is an urgent need to better describe how omicron will impact clinical presentation and vaccine efficacy. This study aims at comparing the epidemiologic, clinical, and genomic characteristics of the omicron variant prevalent during the fifth wave with those of other VOCs between May 2020 and April 2022. Epidemiological data were obtained from the National Electronic Diseases Surveillance System. Secondary data analysis was performed on all confirmed COVID-19 patients. Descriptive data analysis was performed for demographics and patient outcome and the incidence of COVID-19 was calculated as the proportion of SARS-CoV-2 confirmed patients out of the total population of Egypt. Incidence and characteristics of the omicron cohort from January- April 2022, were compared to those confirmed from May 2020-December 2021. We performed the whole-genome sequencing of SARS-CoV-2 on 1590 specimens using Illumina sequencing to describe the circulation of the virus lineages in Egypt. A total of 502,629 patients enrolled, including 60,665 (12.1%) reported in the fifth wave. The incidence rate of omicron was significantly lower than the mean of incidences in the previous subperiod (60.1 vs. 86.3/100,000 population, p < 0.001). Symptoms were reported less often in the omicron cohort than in patients with other variants, with omicron having a lower hospitalization rate and overall case fatality rate as well. The omicron cohort tended to stay fewer days at the hospital than did those with other variants. We analyzed sequences of 2433 (1590 in this study and 843 were obtained from GISAID platform) Egyptian SARS-CoV-2 full genomes. The first wave that occurred before the emergence of global variants of concern belonged to the B.1 clade. The second and third waves were associated with C.36. Waves 4 and 5 included B.1.617.2 and BA.1 clades, respectively. The study indicated that Omicron-infected patients had milder symptoms and were less likely to be hospitalized; however, patients hospitalized with omicron had a more severe course and higher fatality rates than those hospitalized with other variants. Our findings demonstrate the importance of combining epidemiological data and genomic analysis to generate actionable information for public health decision-making.

Backward Bifurcation and Hysteresis in a Mathematical Model of COVID19 with Imperfect Vaccine

Vaccination has been used as strategy to eradicate the spread of COVID-19. But imperfect vaccine has been reported to induce backward bifurcation and hysteresis in mathematical models of disease transmission. Backward bifurcation is a phenomenon whereby a stable endemic equilibrium exists contemporaneously with a stable disease-free equilibrium when the basic reproduction number is less than 1. This situation can cause difficulty in controlling an epidemic because the basic reproduction is no longer the only means of eradicating the disease. In this paper, we propose a mathematical model for the transmission of disease which includes imperfect vaccination. We show that our model is capable of capturing backward bifurcation under certain conditions. By using parameters that are relevant to COVID-19 transmission in Malaysia, our numerical analysis shows that low vaccine efficacy can trigger backward bifurcation.

Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge.

Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly circulating strain and vaccine are mismatched. The novel influenza vaccine platform M2- or BM2-deficient single replication (M2SR and BM2SR) has been shown to safely induce strong systemic and mucosal antibody responses and provide protection against significantly drifted influenza strains. In this study, we demonstrate that both monovalent and quadrivalent (Quad) formulations of M2SR are non-pathogenic in mouse and ferret models, eliciting robust neutralizing and non-neutralizing serum antibody responses to all strains within the formulation. Following challenge with wildtype influenza strains, vaccinated mice and ferrets demonstrated reduced weight loss, decreased viral replication in the upper and lower airways, and enhanced survival as compared to mock control groups. Mice vaccinated with H1N1 M2SR were completely protected from heterosubtypic H3N2 challenge, and BM2SR vaccines provided sterilizing immunity to mice challenged with a cross-lineage influenza B virus. Heterosubtypic cross-protection was also seen in the ferret model, with M2SR vaccinated animals exhibiting decreased viral titers in nasal washes and lungs following the challenge. BM2SR-vaccinated ferrets elicited robust neutralizing antibodies toward significantly drifted past and future influenza B strains. Mice and ferrets that received quadrivalent M2SR were able to mount immune responses equivalent to those seen with each of the four monovalent vaccines, demonstrating the absence of strain interference in the commercially relevant quadrivalent formulation.

Effects of vaccines on clinical characteristics of convalescent adult patients infected with SARS-CoV-2 Omicron variant: A retrospective study.

The protective effect of SARS-CoV-2 vaccines has become a global focus due to Omicron variant pandemic. The effects of various SARS-CoV-2 vaccines are diverse. However, studies on the effect of domestic vaccines on clinical characteristics in convalescent adult patients infected with the Omicron variant are lacking. In this retrospective, single-center cohort study, the effect of three domestic vaccines on clinical characteristics of convalescent adult patients infected with the Omicron variant was investigated in the initial largest outbreak of the Omicron variant infection between January and February 2022 in Tianjin, China. The primary endpoint was COVID-19 severity and the secondary endpoints were re-positive results on nucleic acid tests, liver and kidney function, and inflammation levels during recovery. A total of 320 adult patients infected with the Omicron variant were enrolled, including 296 post-vaccination and 24 unvaccinated patients. The median age of the unvaccinated patients was higher than that of vaccinated patients, but no significant difference was detected in the sex composition ratio between the different groups. Binary logistic regression results suggested that Sinopharm and Sinovac vaccine was an independent protective factor for relieving the severity of the Omicron variant infection. Regrettably, the vaccines did not showed any protective effect on the liver and kidney function of convalescent adult patients. Three domestic vaccines significantly relieved inflammation and increased the SARS-CoV-2-specific antibody levels. Furthermore, Sinovac and CanSino vaccines had a better immune stimulation effect on increasing T lymphocytes levels in convalescent adult patients. In addition, three domestic vaccines have protective effects on preventing re-detectable positive (RP) result in convalescent adult patients. Although the three domestic vaccines cannot prevent the infection of the Omicron variant, it has a significant protective effect in adult patients. This study supports the policy of accelerating to vaccination worldwide combat the evolving and mutating SARS-CoV-2. Omicron spreads faster and might escape antibodies more readily than previous variants, increasing the cases of reinfection and breakthrough infections in vaccinated people. Although vaccinated people are likely to have a much lower risk of severe disease from Omicron infection, many issues still need to be considered. Concerns about lower vaccine efficacy because of new variants might have changed our understanding of the COVID-19 endgame, disabusing the world of the notion that global vaccination is by itself adequate for controlling SARS-CoV-2 infection. The current data showed that vaccination with three domestic SARS-CoV-2 vaccines alleviates the disease severity of adult patients with COVID-19, reduces the inflammation level and the RP rate of convalescent adult patients, and enhances body's defense against the virus in convalescent adult patients. Moreover, our study has highlighted that a combination prevention approach of vaccination and public health measures would be an effective strategy.

Quercetin handles cellular oxidant/antioxidant systems and mitigates immunosenescence hallmarks in human PBMCs: An in vitro study.

Immunosenescence, oxidative stress, and low vaccine efficacy are important symptoms of aging. The goal of our study was to test if quercetin had antiaging and stimulating effects on peripheral blood mononuclear cell(PBMC) immune cells in vitro in the presence of concanavalin a, PBMCs were isolated from healthy elderly and young people and cultured in a complete Roswell Park Memorial Institute 1640 medium supplemented with quercetin. Cell proliferation was assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromidecolorimetric assay after a 48-hincubation period. Spectrophotometricassays were used to assess oxidative biomarkers (proteins carbonyl[PC], malondialdehydes [MDA], and reduced glutathione [GSH]).The enzyme-linkedimmunosorbent assay method was used to determine the amount of interleukin(IL)-2 released. A Griess reagent was used to investigate inducible nitrite oxide synthase(iNOS) activity. When compared to young control cells, aged PBMCs had lower proliferation potency, lower IL-2 and NO release, and higher MDA and PC levels. Importantly, quercetin-treated aged PBMCs have a high proliferative response comparable to young cells, restored iNOS activity, and increased levels of GSH antioxidant defences. In comparison to untreated aged PBMCs, treated PBMCs have lower lipo-oxidative damage but higher PC levels. Quercetin may be used as a promising dietary vaccinal adjuvant in the elderly, it has significant effects in reducing immunosenescence hallmarks, as well as mitigating the lipo-oxidative stress in PBMCs cells.

COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses.

Obesity is a worldwide epidemic and is considered a risk factor of severe manifestation of Coronavirus Disease 2019 (COVID-19). The pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses to infection, re-infection, and vaccination in individuals with obesity remain incompletely understood. Using the diet-induced obese (DIO) mouse model, we studied SARS-CoV-2 Alpha- and Omicron BA.1-induced disease manifestations and host immune responses to infection, re-infection, and COVID-19 mRNA vaccination. Unlike in lean mice, Omicron BA.1 and Alpha replicated to comparable levels in the lungs of DIO mice and resulted in similar degree of tissue damages. Importantly, both T cell and B cell mediated adaptive immune responses to SARS-CoV-2 infection or COVID-19 mRNA vaccination are impaired in DIO mice, leading to higher propensity of re-infection and lower vaccine efficacy. However, despite the absence of neutralizing antibody, vaccinated DIO mice are protected from lung damage upon Omicron challenge, accompanied with significantly more IFN-α and IFN-β production in the lung tissue. Lung RNAseq and subsequent experiments indicated that COVID-19 mRNA vaccination in DIO mice boosted antiviral innate immune response, including the expression of IFN-α, when compared to the nonvaccinated controls. Our findings suggested that COVID-19 mRNA vaccination enhances host innate antiviral responses in obesity which protect the DIO mice to a certain degree when adaptive immunity is suboptimal. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Enablers and barriers to COVID-19 vaccine uptake in an urban slum in Lagos, Nigeria: informing vaccine engagement strategies for the marginalized.

Vaccination against coronavirus disease 2019 (COVID-19) is a cost-effective mitigation strategy against the pandemic. As the COVID-19 vaccine becomes more available, low uptake is now a global threat and understanding the underpinnings in local contexts is a priority for intervention development. We aimed to evaluate behavioural determinants of COVID-19 vaccine acceptance that could inform engagement strategies to improve vaccine uptake in Makoko, an urban slum in Lagos, Nigeria. A population-based case-control study utilized the barrier analysis (BA) approach to evaluate the beliefs and behaviours of 45 'doers' and 45 'non-doers'. The standardized BA tabulation sheet was used to assess differences in the proportions between the two groups to identify significant factors that could be addressed through a behaviour change strategy. Perceived social norms (family, friend, healthcare workers) that approve the vaccine and expected vaccine protection against diseases among doers were determinants of behaviour. Perceived poor accessibility, safety concerns, lack of trust, low vaccine efficacy and low susceptibility to the infection were the most important determinants of behaviour among non-doers. Measures to improve COVID-19 vaccine acceptance in Makoko should include improvement in accessibility and exposing myths and misinformation through clear, concise and evidence-based community education delivered by trusted persons such as healthcare workers and religious leaders.

Stochastic resonance effect observed in a vaccination game with effectiveness framework obeying the SIR process on a scale-free network

This study investigates a standard vaccination game presuming the repeated-season framework, in which we mutually merge the dynamics of disease spread, which obeys the SIR process, and human decision-making as regards whether or not to get vaccinated at the beginning of each season with reference to the evolutionary game theory. We herein presume the Barabási–Albert scale-free (BA-SF) graph as an underlying network. Accordingly, we explore whether or not an additive noise to the transmission rate brings an advantageous stochastic resonance effect for confining a disease's spread. The results show that with a higher vaccination cost and/or a lower vaccine efficacy, the stochastic noise has no gap in vaccination coverage (VC) with the default without noise case, but brings a smaller final epidemic size (FES). In contrast, at a lower vaccination cost and a higher vaccine efficacy, the additive stochastic noise brings a smaller VC that consequently results in a larger FES than the default without noise case. This phenomenon is completely different from our previously reported bolstered enhancement effect of network reciprocity, in which each element of a payoff matrix is exposed to stochastic noise.

The importance of sustained compliance with physical distancing during COVID-19 vaccination rollout

BackgroundIncreasing vaccination coverage against SARS-CoV-2 enabled relaxation of lockdowns in many countries in Europe. As the vaccination rollouts progressed, the public health authorities were seeking recommendations on the continuation of physical distancing measures during ongoing vaccination rollouts. Compliance with these measures was declining while more transmissible virus variants have emerged.MethodsWe used a SARS-CoV-2 transmission model to investigate the feedback between compliance, infection incidence, and vaccination coverage. We quantified our findings in terms of cumulative number of new hospitalisations three and six months after the start of vaccination.ResultsOur results suggest that the combination of fast waning compliance in non-vaccinated individuals, low compliance in vaccinated individuals, low vaccine efficacy against infection and more transmissible virus variants may result in a higher cumulative number of new hospitalisations than in a situation without vaccination. These adverse effects can be alleviated by deploying behavioural interventions that should preferably target both vaccinated and non-vaccinated individuals. The choice of the most appropriate intervention depends on vaccination rate and vaccine efficacy against infection.ConclusionsSupplementary behavioural interventions aiming to boost compliance to physical distancing measures can improve the outcome of vaccination programmes, until vaccination coverage is sufficiently high. For optimal results, these interventions should be selected based on the vaccine efficacy against infection and expected vaccination rate. While we considered the dynamics of SARS-CoV-2, the qualitative effects of the interplay between infectious disease spread and behavior on the outcomes of a vaccination programme can be used as guidance in a future similar pandemic.

A(H3N2) antigenic variation of influenza is associated with low vaccine efficacy in the early 2018 influenza season in Mexico City

ObjectivesWe evaluated the VE and the mutations of the viruses present in the Mexican population at the beginning of 2018. MethodsWe diagnosed influenza in outpatients with a high-performance Rapid Influenza Diagnostic Test (RIDT) qRT–PCR. Descriptive statistics were used to describe the study population, while the chi-square test was used to determine clinical variables. VE was analyzed through a negative test design. We sequenced the hemagglutinin (HA) gene, performed a phylogenetic analysis, and analyzed the nonsynonymous substitutions both in and outside antigenic sites. ResultsOf the 240 patients analyzed, 42.5% received the trivalent vaccine, and 37.5% were positive for influenza. The VE for the general population for any influenza virus type or subtype was 37.0%, while the VE for the predominant influenza A(H3N2) subtype was the lowest (19.7%). The phylogenetic analysis of HA showed the co-circulation of clades and subclades 3C.2a1, 3C.2a1b, 3C.2a2, 3C.2a2re, 3C.2a3, and 3C.3a with identities approximately 97-98% similar to the vaccine composition. ConclusionLow VE was related to the co-circulation of multiple clades and subclades of influenza A(H3N2), with sufficient genetic and phenotypic distance to allow for the infection of vaccinated individuals.

Serial Passaging of Seasonal H3N2 Influenza A/Singapore/G2-31.1/2014 Virus in MDCK-SIAT1 Cells and Primary Chick Embryo Cells Generates HA D457G Mutation and Other Variants in HA, NA, PB1, PB1-F2, and NS1.

Influenza remains one of the most prevalent viruses circulating amongst humans and has resulted in several pandemics. The prevention and control of H3N2 influenza is complicated by its propensity for evolution, which leads to vaccine mismatch and reduced vaccine efficacies. This study employed the strategy of serial passaging to compare the evolution of the human seasonal influenza strain A/Singapore/G2-31.1/2014(H3N2) in MDCK-SIAT1 versus primary chick embryo fibroblast (CEF) cells. Genetic analysis of the HA, NS1, NA, and PB1 gene segments by Sanger sequencing revealed the presence of specific mutations and a repertoire of viral quasispecies following serial passaging. Most quasispecies were also found in PB1, which exhibited consistently high transversion-to-transition ratios in all five MDCK-SIAT1 passages. Most notably, passage 5 virus harbored the D457G substitution in the HA2 subunit, while passage 3 virus acquired K53Q and Q69H mutations in PB1-F2. An A971 variant leading to a non-synonymous R316Q substitution in PB1 was also identified in MDCK-SIAT1 passages 2 and 4. With an increasing number of passages, the proportion of D457G mutations progressively increased and was associated with larger virus plaque sizes. However, microneutralization assays revealed no significant differences in the neutralizing antibody profiles of human-influenza-immune serum samples against pre-passaged virus and passage 5 virus. In contrast, viable virus was only detected in passage 1 of CEF cells, which gave rise to multiple viral RNA quasispecies. Our findings highlight that serial passaging is able to drive differential adaptation of H3N2 influenza in different host species and may alter viral virulence. More studies are warranted to elucidate the complex relationships between H3N2 virus evolution, viral virulence changes, and low vaccine efficacy.

Characterisation of ORF3, M, N and E Gene Sequences of Porcine Epidemic Diarrhoea Virus from Domestic Pigs in Poland.

Porcine epidemic diarrhoea virus (PEDV) is an enteric pathogen causing porcine epidemic diarrhoea and acute gastroenteritis in pigs of all ages. Previous analysis of the viral genome of PEDV in Poland was only based on the spike protein (S) gene sequences and no analysis of other genes has been performed. The aim of this study was to analyse the envelope (E), membrane (M) and nucleocapsid (N) protein and open reading frame 3 (ORF3) gene sequences. Viral RNA from 18 Polish pig faecal samples that were quantitative reverse transcription PCR-positive for PEDV was analysed in four genomic regions (E, M, N and ORF3). Phylogenetic analysis based on these regions' sequences revealed that Polish PEDV isolates were highly related and were clustered into group G2a across the four genes compared. Moreover, the Polish strains were located in distinct subclusters on the phylogenetic trees, which suggests the presence of at least three independently evolving PEDV genetic lines circulating in Poland. The occurrence of unique mutations in the sequences of Polish PEDV strains suggests that PEDV continues to undergo evolutionary processes, accumulating the mutations necessary for viral fitness in its natural hosts. The Polish PEDV strains differed genetically from the CV777 vaccine strain, suggesting the risk of relatively low vaccine efficacy if this strain is used. Our results promote a better understanding of the genetic diversity of PEDV field isolates in Poland and highlight the importance of molecular characterisation of PEDV field strains for the development of an effective vaccine against PEDV.

An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets

There is a crucial need for an improved H3N2 influenza virus vaccine due to low vaccine efficacy rates and increased morbidity and mortality associated with H3N2-dominated influenza seasons. Here, we utilize a computational design strategy to produce epitope-optimized, broadly cross-reactive H3 hemagglutinins in order to create a universal H3N2 influenza vaccine. The Epigraph immunogens are designed to maximize the viral population frequency of epitopes incorporated into the immunogen. We compared our Epigraph H3 vaccine to the traditional egg-based inactivated influenza vaccine from 2018–19, FluZone. Epigraph vaccination-induced stronger cross-reactive antibody responses than FluZone against 18 H3N2 viruses isolated from 1968 to 2019 in both mice and ferrets, with protective hemagglutination inhibition titers against 93–100% of the contemporary H3N2 strains compared to only 27% protection measured from FluZone. In addition, Epigraph vaccination-induced strong cross-reactive T-cell immunity which significantly contributes to protection against lethal influenza virus infection. Finally, Epigraph vaccination protected ferrets from influenza disease after challenge with two H3N2 viruses. The superior cross-reactive immunity induced by these Epigraph immunogens supports their development as a universal H3N2 influenza vaccine.