Seasonal Vaccine Research Articles

Correlation of long-term care facility vaccination practices between seasons and resident types

BackgroundInfluenza vaccination varies widely across long-term care facilities (LTCFs) due to staff behaviors, LTCF practices, and patient factors. It is unclear how seasonal LTCF vaccination varies between cohabitating but distinct short-stay and long-stay residents. Thus, we assessed the correlation of LTCF vaccination between these populations and across seasons.MethodsThe study design is a national retrospective cohort using Medicare and Minimum Data Set (MDS) data. Participants include U.S. LTCFs. Short-stay and long-stay Medicare-enrolled residents age ≥ 65 in U.S. LTCFs from a source population of residents during October 1st-March 31st in 2013–2014 (3,042,881 residents; 15,683 LTCFs) and 2014–2015 (3,143,174, residents; 15,667 LTCFs). MDS-assessed influenza vaccination was the outcome. Pearson correlation coefficients were estimated to assess seasonal correlations between short-stay and long-stay resident vaccination within LTCFs.ResultsThe median proportion of short-stay residents vaccinated across LTCFs was 70.4% (IQR, 50.0–82.7%) in 2013–2014 and 69.6% (IQR, 50.0–81.6%) in 2014–2015. The median proportion of long-stay residents vaccinated across LTCFs was 85.5% (IQR, 78.0–90.9%) in 2013–2014 and 84.6% (IQR, 76.6–90.3%) in 2014–2015. Within LTCFs, there was a moderate correlation between short-stay and long-stay vaccination in 2013–2014 (r = 0.50, 95%CI: 0.49–0.51) and 2014–2015 (r = 0.53, 95%CI: 0.51–0.54). Across seasons, there was a moderate correlation for LTCFs with short-stay residents (r = 0.54, 95%CI: 0.53–0.55) and a strong correlation for those with long-stay residents (r = 0.68, 95%CI: 0.67–0.69).ConclusionsIn LTCFs with inconsistent influenza vaccination across seasons or between populations, targeted vaccination protocols for all residents, regardless of stay type, may improve successful vaccination in this vulnerable patient population.

Antigenic Characterization and Pandemic Risk Assessment of North American H1 Influenza A Viruses Circulating in Swine.

The first pandemic of the 21st century was caused by an H1N1 influenza A virus (IAV) introduced from pigs into humans, highlighting the importance of swine as reservoirs for pandemic viruses. Two major lineages of swine H1 circulate in North America: the 1A classical swine lineage (including that of the 2009 H1N1 pandemic) and the 1B human seasonal-like lineage. Here, we investigated the evolution of these H1 IAV lineages in North American swine and their potential pandemic risk. We assessed the antigenic distance between the HA of representative swine H1 and human seasonal vaccine strains (1978 to 2015) in hemagglutination inhibition (HI) assays using a panel of monovalent antisera raised in pigs. Antigenic cross-reactivity varied by strain but was associated with genetic distance. Generally, the swine 1A lineage viruses that seeded the 2009 H1 pandemic were antigenically most similar to the H1 pandemic vaccine strains, with the exception of viruses in the genetic clade 1A.1.1.3, which had a two-amino acid deletion mutation near the receptor-binding site, which dramatically reduced antibody recognition. The swine 1B lineage strains, which arose from previously circulating (pre-2009 pandemic) human seasonal viruses, were more antigenically similar to pre-2009 human seasonal H1 vaccine viruses than post-2009 strains. Human population immunity was measured by cross-reactivity in HI assays to representative swine H1 strains. There was a broad range of titers against each swine strain that was not associated with age, sex, or location. However, there was almost no cross-reactivity in human sera to the 1A.1.1.3 and 1B.2.1 genetic clades of swine viruses, and the 1A.1.1.3 and 1B.2.1 clades were also the most antigenically distant to the human vaccine strains. Our data demonstrate that the antigenic distances of representative swine strains from human vaccine strains represent an important part of the rational assessment of swine IAV for zoonotic risk research and pandemic preparedness prioritization. IMPORTANCE Human H1 influenza A viruses (IAV) spread to pigs in North America, resulting in a sustained circulation of two major groups of H1 viruses in swine. We quantified the genetic diversity of H1 in swine and measured antigenic phenotypes. We demonstrated that the swine H1 lineages were significantly different from the human vaccine strains and that this antigenic dissimilarity increased over time as the viruses evolved in swine. Pandemic preparedness vaccine strains for human vaccines also demonstrated a loss in similarity with contemporary swine strains. Human sera revealed a range of responses to swine IAV, including two groups of viruses with little to no immunity. The surveillance and risk assessment of IAV diversity in pig populations are essential to detect strains with reduced immunity in humans and provide critical information for pandemic preparedness.

Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity.

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03A; 2. inactivated vaccine with 5.75 μg HA/dose + AS03A; 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).

Interspecies Transmission from Pigs to Ferrets of Antigenically Distinct Swine H1 Influenza A Viruses with Reduced Reactivity to Candidate Vaccine Virus Antisera as Measures of Relative Zoonotic Risk.

During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population. To prepare for the potential of a future swine-origin IAV pandemic in humans, public health laboratories selected candidate vaccine viruses (CVV) for use as vaccine seed strains. To assess the pandemic risk of contemporary US swine H1N1 or H1N2 strains, we quantified the genetic diversity of swine H1 HA genes, and identified representative strains from each circulating clade. We then characterized the representative swine IAV against human seasonal vaccine and CVV strains using ferret antisera in hemagglutination inhibition assays (HI). HI assays revealed that 1A.3.3.2 (pdm09) and 1B.2.1 (delta-2) demonstrated strong cross reactivity to human seasonal vaccines or CVVs. However, swine IAV from three clades that represent more than 50% of the detected swine IAVs in the USA showed significant reduction in cross-reactivity compared to the closest CVV virus: 1A.1.1.3 (alpha-deletion), 1A.3.3.3-clade 3 (gamma), and 1B.2.2.1 (delta-1a). Representative viruses from these three clades were further characterized in a pig-to-ferret transmission model and shown to exhibit variable transmission efficiency. Our data prioritize specific genotypes of swine H1N1 and H1N2 to further investigate in the risk they pose to the human population.

Predicted effectiveness of vaccines and extended half-life monoclonal antibodies against RSV hospitalizations in children

Several vaccines and extended half-life monoclonal antibodies (mAbs) against respiratory syncytial virus (RSV) have shown promise in clinical trials. We used age-structured transmission models to predict the possible impact of various RSV prevention strategies including maternal immunization, live-attenuated vaccines, and long-lasting mAbs. Our results suggest that maternal immunization and long-lasting mAbs are likely to be highly effective in preventing RSV hospitalizations in infants under 6 months of age, averting more than half of RSV hospitalizations in neonates. Live-attenuated vaccines could reduce RSV hospitalizations in vaccinated age groups and are also predicted to have a modest effect in unvaccinated age groups because of disruptions to transmission. Compared to year-round vaccination, a seasonal vaccination program at the country level provides at most a minor advantage regarding efficiency. Our findings highlight the substantial public health impact that upcoming RSV prevention strategies may provide.

Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice

Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that a suboptimial usage of population-wide universal influenza vaccine may drive formation of escape variants attributed to polygenic changes.

Flu and Covid-19: is there adherence to vaccination in target groups?

Abstract Background In Italy, the flu vaccine is recommended and free for target groups (adults≥60 years old, fragile people, healthcare workers, pregnant women). During the 2020/2021 flu season, an increased vaccination coverage (+6,9%) was observed compared to the previous season, also due to the Covid-19 pandemic. We aimed to investigate how strong the adherence to the flu vaccine was by the vulnerable groups and assess if the Covid-19 vaccination campaign may have influenced the rate of flu vaccines. Methods At the beginning of autumn 2021 we conducted an online survey among the population of Tuscany. We collected data on demographics, health status (pregnancy, vulnerable), flu and COVID-19 vaccinations coverage and health information sources. In addition, we performed a descriptive and a risk factors analysis to assess correlation between our variables with R v 4.0.0. Significance level was set at p < 0.05. Results Among 408 participants, 248 (61%) belong to a vulnerable group and are recommended to receive the flu vaccine, 229 (56%) usually get the flu vaccine, 386 (95%) got the Covid-19 vaccine, 267 (65%) choose and trust the general practitioner (GP) as their health information source. There is a statistically significant association between being part of a vulnerable group and getting the seasonal flu vaccine (OR 6.63 95% CI 4.26-10.3 p < 0.001). In addition, getting the Covid-19 vaccine increases the likelihood of receiving the flu vaccine (2.90 95% CI 1.16-7.28 p = 0.018). Moreover, participants who trust their GP as their health information source (OR 1.63 CI 1.08-2.46 p = 0.019) are more likely to receive the flu vaccine; other information sources (TV, newspaper, social media) are not associated with the flu vaccine. Conclusions Our research shows that vulnerable groups get vaccinated against the flu. The increase in flu vaccine coverage may be due to the COVID-19 vaccines campaign. GPs play a crucial role in the health promotion, prevention and health literacy of patients. Key messages

Original antigen sin and COVID-19: implications for seasonal vaccination

ABSTRACT Introduction Original antigenic sin describes the phenomenon in which immunity against pathogens or antigens is shaped by the host’s first exposure to a related pathogen or antigen. Areas covered When primary immunity is boosted not by the homologous but by a cross-reacting vaccine, the newly formed antibodies may react better with the primary antigen than with the antigen actually eliciting the response. This form of immune imprinting, which has been observed with influenza, dengue, human immunodeficiency virus, and other pathogens, has profound implications for the approach to seasonal vaccination against a variety of diseases, including COVID-19. Expert opinion Public health agencies and regulatory bodies have consistently recommended repeated vaccinations every few months as a way to protect against COVID-19. However, the risks and benefits of this approach require scrutiny given the concern for original antigenic sin in response to SARS-CoV-2. This manuscript examines what is known about immune imprinting and looks ahead to explore how this phenomenon may impact seasonal vaccination against emerging SARS-CoV-2 subvariants such as BA.4, BA.5, and BA.5.1, which have been associated with increased transmissibility due to enhanced immune escape.

Influenza During the 2010-2020 Decade in the United States: Seasonal Outbreaks and Vaccine Interventions.

The 10 years between the last influenza pandemic and start of the severe acute respiratory syndrome coronavirus 2 pandemic have been marked by great advances in our ability to follow influenza occurrence and determine vaccine effectiveness (VE), largely based on widespread use of the polymerase chain reaction assay. We examine the results, focusing mainly on data from the United States and inactivated vaccines. Surveillance has expanded, resulting in increased ability to characterize circulating viruses and their impact. The surveillance has often confirmed previous observations on timing of outbreaks and age groups affected, which can now be examined in greater detail. Selection of strains for vaccines is now based on enhanced viral characterization using immunologic, virologic, and computational techniques not previously available. Vaccine coverage has been largely stable, but VE has remained modest and, in some years, very low. We discuss ways to improve VE based on existing technology while we work toward supraseasonal vaccines.

The Application and Outcome Evaluation of a Social Marketing Intervention to Increase Seasonal Influenza Vaccination among University Students.

Seasonal flu vaccination rates among university students are exceedingly low and research focused on voluntarily influencing vaccination uptake is limited. This study outlines the development, implementation, and evaluation of a theory-driven social marketing vaccination intervention following the co-create-build-engage (CBE) framework. This study drew upon a pre-intervention segmentation study and co-created interventions targeted at receptive segments. The intervention delivered a significant 343% increase in vaccination rates using a difference-in-difference analysis. Online communication channels effectively engaged students to register for and receive their flu vaccine Almost 90% of students who received vaccinations signed up in the first two weeks of the intervention program indicating that those who can be motivated will act early in the flu season. Financial incentives, as found in previous studies, were confirmed as highly effective in increasing awareness and influencing vaccination uptake behaviours. Friend referral incentives were also found to be influential in motivating vaccination uptake. Suggestions are provided for future research and practical implementation of interventions on university campuses to motivate flu vaccination and other health behaviours.

The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone

BackgroundA recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria.MethodsIn order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes.ResultsThe overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2–3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks.ConclusionsThe efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems.Trial registrationThe RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218

Strategies targeting hemagglutinin cocktail as a potential universal influenza vaccine.

Vaccination is the most effective means of protecting people from influenza virus infection. The effectiveness of existing vaccines is very limited due to antigenic drift of the influenza virus. Therefore, there is a requirement to develop a universal vaccine that provides broad and long-lasting protection against influenza. CD8+ T-cell response played a vital role in controlling influenza virus infection, reducing viral load, and less clinical syndrome. In this study, we optimized the HA sequences of human seasonal influenza viruses (H1N1, H3N2, Victoria, and Yamagata) by designing multivalent vaccine antigen sets using a mosaic vaccine design strategy and genetic algorithms, and designed an HA mosaic cocktail containing the most potential CTL epitopes of seasonal influenza viruses. We then tested the recombinant mosaic antigen, which has a significant number of potential T-cell epitopes. Results from genetic evolutionary analyses and 3D structural simulations demonstrated its potential to be an effective immunogen. In addition, we have modified an existing neutralizing antibody-based seasonal influenza virus vaccine to include a component that activates cross-protective T cells, which would provide an attractive strategy for improving human protection against seasonal influenza virus drift and mutation and provide an idea for the development of a rationally designed influenza vaccine targeting T lymphocyte immunity.

Analysis of Infections Caused by Influenza Viruses and Influenza-Like Viruses in the Population of People over 65 Years of Age in the 2019-2020 Epidemic Season in Poland.

BACKGROUND Influenza can be the most dangerous for people in risk groups, for example for seniors, in whom it can lead to serious and life-threatening complications. The aim of this research was to analyze the activity of influenza viruses and influenza-like viruses in patients over 65 years of age in the 2019-2020 epidemic season in Poland. MATERIAL AND METHODS A total of 1269 samples collected from patients over 65 years of age with suspected influenza or other respiratory viruses in the 2019-2020 epidemic season (from October 1, 2019, to September 30, 2020) were analyzed. The test material was nose and throat swabs collected during the 2019-2020 epidemic season. Quantitative polymerase chain reaction was used to determine the influenza virus type and subtype for positive samples. RESULTS Among the confirmed infections with influenza viruses, cases due to influenza A were dominant, and the dominant subtype was influenza A subtype A/H1N1/pdm09. Infections with influenza-like viruses were also confirmed in the patients participating in the study, with the presence of genetic material of respiratory syncytial viruses confirmed most often. CONCLUSIONS Seasonal vaccinations can significantly reduce the number of cases and thus the risk of post-influenza complications and deaths among seniors. This is very important, especially now, due to the current epidemiological situation related to the ongoing SARS-CoV-2 respiratory virus pandemic.

Antiviral Peptides as Anti-Influenza Agents.

Influenza viruses represent a leading cause of high morbidity and mortality worldwide. Approaches for fighting flu are seasonal vaccines and some antiviral drugs. The development of the seasonal flu vaccine requires a great deal of effort, as careful studies are needed to select the strains to be included in each year’s vaccine. Antiviral drugs available against Influenza virus infections have certain limitations due to the increased resistance rate and negative side effects. The highly mutative nature of these viruses leads to the emergence of new antigenic variants, against which the urgent development of new approaches for antiviral therapy is needed. Among these approaches, one of the emerging new fields of “peptide-based therapies” against Influenza viruses is being explored and looks promising. This review describes the recent findings on the antiviral activity, mechanism of action and therapeutic capability of antiviral peptides that bind HA, NA, PB1, and M2 as a means of countering Influenza virus infection.

Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis

Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We aimed to estimate the reduction in vaccine effectiveness associated with repeated influenza vaccination. In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and CINAHL Complete databases for articles published from Jan 1, 2016, to June 13, 2022, and Web of Science for studies published from database inception to June 13, 2022. For studies published before Jan 1, 2016, we consulted published systematic reviews. Two reviewers (EJ-G and EJR) independently screened, extracted data using a data collection form, assessed studies' risk of bias using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) and evaluated the weight of evidence by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included observational studies and randomised controlled trials that reported vaccine effectiveness against influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B using four vaccination groups: current season; previous season; current and previous seasons; and neither season (reference). For each study, we calculated the absolute difference in vaccine effectiveness (ΔVE) for current season only and previous season only versus current and previous season vaccination to estimate attenuation associated with repeated vaccination. Pooled vaccine effectiveness and ∆VE were calculated by season, age group, and overall. This study is registered with PROSPERO, CRD42021260242. We identified 4979 publications, selected 681 for full review, and included 83 in the systematic review and 41 in meta-analyses. ΔVE for vaccination in both seasons compared with the current season was -9% (95% CI -16 to -1, I2=0%; low certainty) for influenza A(H1N1)pdm09, -18% (-26 to -11, I2=7%; low certainty) for influenza A(H3N2), and -7% (-14 to 0, I2=0%; low certainty) for influenza B, indicating lower protection with consecutive vaccination. However, for all types, A subtypes and B lineages, vaccination in both seasons afforded better protection than not being vaccinated. Our estimates suggest that, although vaccination in the previous year attenuates vaccine effectiveness, vaccination in two consecutive years provides better protection than does no vaccination. The estimated effects of vaccination in the previous year are concerning and warrant additional investigation, but are not consistent or severe enough to support an alternative vaccination regimen at this time. WHO and the US National Institutes of Health.

Declining influenza vaccination rates in an underserved pediatric primary care center during the COVID-19 pandemic

BackgroundInfluenza vaccination rates are decreasing in the United States. Disinformation surrounding COVID-related public health protections and SARS-CoV-2 vaccine roll-out may have unintended consequences impacting pediatric influenza vaccination.We assessed influenza vaccination rates before and during the COVID-19 pandemic in one pediatric primary care center, serving a minoritized population. MethodsA cross-sectional study assessed influenza vaccination rates for children aged 6 months to 12 years over the following influenza seasons (September-May): 1) 2018–19 and 2019–20 (pre-pandemic), and 2) 2020–21 and 2021–22 (intra-pandemic). Demographics and responses to social risk questionnaires were extracted from electronic health records. Total tetanus vaccinations across influenza seasons served as approximations of general vaccination rates. Generalized linear regression models with robust standard errors evaluated differences in demographics, social risks, and influenza vaccination rates by season. Multivariable logistic regression with robust standard errors evaluated associations between influenza season, demographics, social risks, and influenza vaccination. ResultsMost patients were young (mean age ∼ 6 years), non-Hispanic Black (∼80%), and publicly insured (∼90%). Forty-two percent of patients eligible to receive the influenza vaccine who were seen in 2019–20 influenza season received the influenza vaccine, compared to 30% in 2021–22. Influenza and tetanus vaccination rates decreased during the COVID-19 pandemic (p < 0.01). The 2020–21 and 2021–22 influenza seasons, older age, Black race, and self-pay were associated with decreased influenza vaccine administration (p < 0.05). ConclusionsInfluenza vaccination rates within one pediatric primary care center decreased during the COVID-19 pandemic and have not rebounded, particularly for older children, those identifying as Black, and those without insurance.

Murine Broadly Reactive Antineuraminidase Monoclonal Antibodies Protect Mice from Recent Influenza B Virus Isolates and Partially Inhibit Virus Transmission in the Guinea Pig Model.

ABSTRACTCurrent influenza virus vaccines and antivirals have limitations, some of which disproportionately affect their utilization against influenza B viruses. To inform ongoing efforts to address the considerable global burden of influenza B viruses, we previously described five murine monoclonal antibodies that broadly bind conserved epitopes on the neuraminidase of influenza B viruses and protect against lethal challenge in a mouse model when delivered via intraperitoneal injection. Here, we validate the continued relevance of these antibodies by demonstrating that their protective effects extend to lethal challenge with mouse-adapted influenza B viruses recently isolated from humans. We also found that humanization of murine antibodies 1F2 and 4F11 resulted in molecules that retain the ability to protect mice from lethal challenge when administered prophylactically. Intranasal administration as an alternative route of 1F2 delivery revealed no differences in the mouse challenge model compared to intraperitoneal injection, supporting further assessment of this more targeted and convenient administration method. Lastly, we evaluated the potential for intranasal 1F2 administration initiated 1 day after infection to prevent transmission of an influenza B virus between cocaged guinea pigs. Here, we observed a 40% rate of transmission with the 1F2 antibody administered to the infected donor compared to 100% transmission with administration of an irrelevant control antibody. These data suggest that intranasal administration could be a viable route of administration for antibody therapeutics. Collectively, these findings demonstrate the potential of broad antineuraminidase antibodies as therapeutics to prevent and treat infections caused by influenza B viruses.IMPORTANCE The global health burden of influenza B viruses, especially in children, has long been underappreciated. Although two antigenically distinct influenza B virus lineages cocirculated before the coronavirus disease 2019 (COVID-19) pandemic, the commonly used trivalent seasonal vaccines contain antigens from only one influenza B virus, providing limited cross-protection against viruses of the other lineage. Additionally, studies have called into question the clinical effectiveness of the neuraminidase inhibitors that comprise the majority of available antivirals in treating influenza B virus infections. We previously described antibodies that bind broadly to neuraminidases of influenza B viruses across decades of antigenic evolution and potently protect mice against lethal challenge. Here we appraise additional factors to develop these antineuraminidase antibodies as antivirals to prevent and treat infections caused by an extensive range of influenza B viruses. In addition this work assesses recent clinical isolates belonging to the two influenza B virus lineages, finding evidence supporting the development of these antibodies for prophylactic and therapeutic use.

Understanding the dynamic relation between wastewater SARS-CoV-2 signal and clinical metrics throughout the pandemic

Wastewater surveillance (WWS) of SARS-CoV-2 was proven to be a reliable and complementary tool for population-wide monitoring of COVID-19 disease incidence but was not as rigorously explored as an indicator for disease burden throughout the pandemic. Prior to global mass immunization campaigns and during the spread of the wildtype COVID-19 and the Alpha variant of concern (VOC), viral measurement of SARS-CoV-2 in wastewater was a leading indicator for both COVID-19 incidence and disease burden in communities. As the two-dose vaccination rates escalated during the spread of the Delta VOC in Jul. 2021 through Dec. 2021, relations weakened between wastewater signal and community COVID-19 disease incidence and maintained a strong relationship with clinical metrics indicative of disease burden (new hospital admissions, ICU admissions, and deaths). Further, with the onset of the vaccine-resistant Omicron BA.1 VOC in Dec. 2021 through Mar. 2022, wastewater again became a strong indicator of both disease incidence and burden during a period of limited natural immunization (no recent infection), vaccine escape, and waned vaccine effectiveness. Lastly, with the populations regaining enhanced natural and vaccination immunization shortly prior to the onset of the Omicron BA.2 VOC in mid-Mar 2022, wastewater is shown to be a strong indicator for both disease incidence and burden. Hospitalization-to-wastewater ratio is further shown to be a good indicator of VOC virulence when widespread clinical testing is limited. In the future, WWS is expected to show moderate indication of incidence and strong indication of disease burden in the community during future potential seasonal vaccination campaigns.

The baculovirus expression vector system: a modern technology for the future of influenza vaccine manufacturing

Introduction Influenza is a vaccine-preventable disease. Due to the evolving nature of influenza viruses, the composition of vaccines has to be updated annually. Most of the current influenza vaccines are still produced in embryonated chicken eggs, a well-established process with some limitations. Area covered This review focuses on the recombinant DNA technology using baculovirus expression vector system a modern method of manufacturing licensed influenza vaccines. The speed, scalability, biosafety and flexibility of the process, together with the reliability of the haemagglutinin in the vaccine, represent a significant advance towards new platforms for vaccine production. Expert opinion The scenario of vaccine production in the next years seems to be particularly interesting, involving a transition from the current egg-based production to new technologies, such as the cell culture platform, the RNA technology, the plant-based system, and the DNA vaccine. This latter offers great advantages over egg- and cell-based influenza vaccine production. The universal vaccine remains the goal of researchers and ideally would avoid the need for annual reformulation and re-administration of seasonal vaccines. The lesson learned from the COVID-19 pandemic highlights the importance of having different technologies available and able to promptly respond to a great demand of vaccines worldwide.

Could seasonal Influenza virus vaccine reduce the risk and severity Of SARS-CoV-2 infection? - The first Egyptian experience

Could seasonal Influenza virus vaccine reduce the risk and severity Of SARS-CoV-2 infection? - The first Egyptian experience