End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain.

BACKGROUND: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. METHODS: End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. METHODS: Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: -6% to 54%). VE for those aged 18-64, who largely received cell-based vaccines, was 47% (95% CI: 37%-56%). Overall VE for 2-17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%-76%). CONCLUSION: The paper provides evidence of moderate influenza VE in 2022/23.

Prevalence of circulating antibodies against hemagglutinin of influenza viruses in epidemic season 2021/2022 in Poland.

The aim of the study was to determine the level of anti-hemagglutinin antibodies in the serum of patients during the 2021/2022 epidemic season in Poland. A total of 700 sera samples were tested, divided according to the age of the patients into 7 age groups: 0-4 years of age, 5-9 years of age, 10-14 years of age, 15-25 years of age, 26-44 years of age, 45-64 years of age and ≥65 years of age, 100 samples were collected from each age group. Anti-hemagglutinin antibody levels was determined using the haemagglutination inhibition assay (OZHA). The results obtained confirm the presence of anti-hemagglutinin antibodies for the antigens A/Victoria/2570/2019 (H1N1) pdm09, A/Cambodia/e0826360/2020 (H3N2), B/Washington/02/2019 and B/Phuket/3073/2013 recommended by World Health Organization (WHO) for the 2021/2022 epidemic season. The analysis of the results shows differences in the levels of individual anti-hemagglutinin antibodies in the considered age groups. In view of very low percentage of the vaccinated population in Poland, which was 6.90% in the 2021/2022 epidemic season, the results obtained in the study would have to be interpreted as the immune system response in patients after a previous influenza virus infection.

Seroprevalence of Protective Antibodies Against Influenza and the Reduction of the Influenza Incidence Rate: An Annual Repeated Cross-Sectional Study From 2014 to 2019.

BACKGROUND: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate. METHODS: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal. A total of 4326 sera from all age groups, sex, and regions was tested by hemagglutination inhibition assay. Seroprevalence and geometric mean titers (GMT) of protective antibodies against influenza were assessed by age group, sex, and vaccine status (65+ years old). The association between summer annual seroprevalence and the difference of influenza incidence rates between one season and the previous one was measured by Pearson correlation coefficient (r). RESULTS: Significant differences in seroprevalence of protective antibodies against influenza were observed in the population. Higher seroprevalence and GMT for A(H1N1)pdm09 and A(H3N2) were observed in children (5-14); influenza B seroprevalence in adults 65+ was 1.6-4.4 times than in children (0-4). Vaccinated participants (65+) showed significant higher seroprevalence/GMT for influenza. A strong negative and significant correlation was found between seroprevalence and ILI incidence rate for A(H1N1)pdm09 in children between 5 and 14 (r = -0.84; 95% CI, -0.98 to -0.07); a weak negative correlation was observed for A(H3N2) and B/Yamagata (r ≤ -0.1). CONCLUSIONS: The study provides new insight into the anti-influenza antibodies seroprevalence measured in summer on the ILI incidence rate in the next season and the need for adjusted preventive health care measures to prevent influenza infection and transmission.

CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age.

Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8+ T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8+ T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer+CD8+ T-cells are present within blood and tissues. Frequencies of IBV-specific CD8+ T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP30-38 epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1196-206 (11-mer) and HLA-B*07:02-restricted NP30-38 epitope presentation. Our study increases the number of IBV CD8+ T-cell epitopes, and defines IBV-specific CD8+ T-cells at cellular and molecular levels, across tissues and age.

A live attenuated influenza B virus vaccine expressing RBD elicits protective immunity against SARS-CoV-2 in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.

Evaluation of CLINITEST® Rapid Covid-19 + Influenza antigen test in a cohort of symptomatic patients in an emergency department.

OBJECTIVES: Rapid management of patients with respiratory tract infections in hospital emergency departments is one of the main objectives since the concurrent circulation of respiratory viruses following the SARS-CoV-2 pandemic. The use of new combined point-of-care antigen tests for detecting influenza A/B and SARS-CoV-2 represents an advantage in response time over the molecular tests. The objective was to evaluate the suitability of the CLINITEST® Rapid Covid-19 + Influenza Antigen test (Siemens Healthineers, Germany) (RCIA test) by measuring the sensitivity, specificity, Cohen's kappa, and cut-off values. METHODS: Nasopharyngeal samples were collected from a randomised group of symptomatic patients of all ages at emergency department during January-February 2023. In parallel, these patients were screened for influenza A/B, and SARS-CoV-2 using RT-PCR. The Ct (cycle threshold) values were collected for positive [RT-PCR (+) /RCIA test (+)] and false negative [(RT-PCR (+) /RCIA test (-)] samples. A subanalysis was performed in the paediatric population (< 16 years-old). RESULTS: We included 545 patients (55.8% females) with a median age of 7 years-old (IQR: 1-66.5). The RCIA test showed a sensitivity of 59.7% [95%CI: 46.9-67.33] for influenza A, 65.6% [95%CI: 49.5-80.3] for influenza B, and 76.9% [95%CI: 45.8-84.8] for SARS-CoV-2. The specificity was between 90.7%-99.7% with a moderate/high level of agreement with RT-PCR (kappa score: 0.6-0.8) for the three respiratory viruses included in the RCIA test. CONCLUSIONS: The sensitivity of the RCIA test is insufficient for screening of patients, including patients with low Ct values (Ct > 20). Despite its good specificity and Cohen's kappa value, its use as a screening test is not comparable to RT-PCR systems in the ED environment with a high number of false negative results.

Differential interferon responses to influenza A and B viruses in primary ferret respiratory epithelial cells.

Influenza B viruses (IBV) cocirculate with influenza A viruses (IAV) and cause periodic epidemics of disease, yet antibody and cellular responses following IBV infection are less well understood. Using the ferret model for antisera generation for influenza surveillance purposes, IAV resulted in robust antibody responses following infection, whereas IBV required an additional booster dose, over 85% of the time, to generate equivalent antibody titers. In this study, we utilized primary differentiated ferret nasal epithelial cells (FNECs) which were inoculated with IAV and IBV to study differences in innate immune responses which may result in differences in adaptive immune responses in the host. FNECs were inoculated with IAV (H1N1pdm09 and H3N2 subtypes) or IBV (B/Victoria and B/Yamagata lineages) and assessed for 72 h. Cells were analyzed for gene expression by quantitative real-time PCR, and apical and basolateral supernatants were assessed for virus kinetics and interferon (IFN), respectively. Similar virus kinetics were observed with IAV and IBV in FNECs. A comparison of gene expression and protein secretion profiles demonstrated that IBV-inoculated FNEC expressed delayed type-I/II IFN responses and reduced type-III IFN secretion compared to IAV-inoculated cells. Concurrently, gene expression of Thymic Stromal Lymphopoietin (TSLP), a type-III IFN-induced gene that enhances adaptive immune responses, was significantly downregulated in IBV-inoculated FNECs. Significant differences in other proinflammatory and adaptive genes were suppressed and delayed following IBV inoculation. Following IBV infection, ex vivo cell cultures derived from the ferret upper respiratory tract exhibited reduced and delayed innate responses which may contribute to reduced antibody responses in vivo.IMPORTANCEInfluenza B viruses (IBV) represent nearly one-quarter of all human influenza cases and are responsible for significant clinical and socioeconomic impacts but do not pose the same pandemic risks as influenza A viruses (IAV) and have thus received much less attention. IBV accounts for greater severity and deaths in children, and vaccine efficacy remains low. The ferret can be readily infected with human clinical isolates and demonstrates a similar course of disease and immune responses. IBV, however, generates lower antibodies in ferrets than IAV following the challenge. To determine whether differences in initial innate responses following infection may affect the development of robust adaptive immune responses, ferret respiratory tract cells were isolated, infected with IAV/IBV, and compared. Understanding the differences in the initial innate immune responses to IAV and IBV may be important in the development of more effective vaccines and interventions to generate more robust protective immune responses.

A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.

Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes.

Seasonal influenza vaccines offer little protection against pandemic influenza virus strains. It is difficult to create effective prepandemic vaccines because it is uncertain which influenza virus subtype will cause the next pandemic. In this work, we developed a nucleoside-modified messenger RNA (mRNA)-lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A virus subtypes and influenza B virus lineages. This multivalent vaccine elicited high levels of cross-reactive and subtype-specific antibodies in mice and ferrets that reacted to all 20 encoded antigens. Vaccination protected mice and ferrets challenged with matched and mismatched viral strains, and this protection was at least partially dependent on antibodies. Our studies indicate that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens.

The influenza universe in an mRNA vaccine.

An mRNA-lipid nanoparticle vaccine protects animals from 20 influenza lineages.

Interim Estimates of 2021-22 Seasonal Influenza Vaccine Effectiveness - United States, February 2022.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.

Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model.

H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.

Mosaic Hemagglutinin-Based Whole Inactivated Virus Vaccines Induce Broad Protection Against Influenza B Virus Challenge in Mice.

Influenza viruses undergo antigenic changes in the immuno-dominant hemagglutinin (HA) head domain, necessitating annual re-formulation of and re-vaccination with seasonal influenza virus vaccines for continuing protection. We previously synthesized mosaic HA (mHA) proteins of influenza B viruses which redirect the immune response towards the immuno-subdominant conserved epitopes of the HA via sequential immunization. As ~90% of current influenza virus vaccines are manufactured using the inactivated virus platform, we generated and sequentially vaccinated mice with inactivated influenza B viruses displaying either the homologous (same B HA backbones) or the heterologous (different B HA backbones) mosaic HAs. Both approaches induced long-lasting and cross-protective antibody responses showing strong antibody-dependent cellular cytotoxicity (ADCC) activity. We believe the B virus mHA vaccine candidates represent a major step towards a universal influenza B virus vaccine.

Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus.

A panel of influenza virus-like sequences were recently documented in fish and amphibians. Of these, the Wuhan spiny eel influenza virus (WSEIV) was found to phylogenetically cluster with influenza B viruses as a sister clade. Influenza B viruses have been documented to circulate only in humans, with certain virus isolates found in harbor seals. It is therefore interesting that a similar virus was potentially found in fish. Here we characterize the putative hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of the WSEIV. Functionally, we show that the WSEIV NA-like protein has sialidase activity comparable to B/Malaysia/2506/2004 influenza B virus NA, making it a bona fide neuraminidase that is sensitive to NA inhibitors. We tested the functionality of the HA by addressing the receptor specificity, stability, preferential airway protease cleavage, and fusogenicity. We show highly specific binding to monosialic ganglioside 2 (GM2) and fusogenicity at a range of different pH conditions. In addition, we found limited antigenic conservation of the WSEIV HA and NA relative to the B/Malaysia/2506/2004 virus HA and NA. In summary, we perform a functional and antigenic characterization of the glycoproteins of WSEIV to assess if it is indeed a bona fide influenza virus potentially circulating in ray-finned fish.

Prevalence of antibodies against seasonal influenza A and B viruses among older adults in rural Thailand: A cross-sectional study.

Assessing the seroprevalence of the high-risk individuals against the influenza virus is essential to evaluate the progress of vaccine implementation programs and establish influenza virus interventions. Herein, we identified the pre-existing cross-protection of the circulating seasonal influenza viruses among the older-aged population. A cross-sectional study was performed base on the 176 residual sera samples collected from older adults aged 60 to 95 years without a history of vaccination in rural Thailand in 2015. Sera antibody titers against influenza A and B viruses circulating between 2016 and 2019 were determined by hemagglutination inhibition assay. These findings indicated the low titers of pre-existing antibodies to circulating influenza subtypes and showed age-independent antibody titers among the old adults. Moderate seropositive rates (HAI ≥ 1:40) were observed in influenza A viruses (65.9%A(H3N2), 50.0% for A(H1N1) pdm09), and found comparatively lower rates in influenza B viruses (14% B/Yam2, 21% B/Yam3 and 25% B/Vic). Only 5% of individuals possessed broadly protective antibodies against both seasonal influenza A and B virus in this region. Our findings highlighted the low pre-existing antibodies to circulating influenza strains in the following season observed in older adults. The serological study will help inform policy-makers for health care planning and guide control measures concerning vaccination programs.

A New Master Donor Virus for the Development of Live-Attenuated Influenza B Virus Vaccines.

Influenza B viruses (IBV) circulate annually, with young children, the elderly and immunocompromised individuals being at high risk. Yearly vaccinations are recommended to protect against seasonally influenza viruses, including IBV. Live attenuated influenza vaccines (LAIV) provide the unique opportunity for direct exposure to the antigenically variable surface glycoproteins as well as the more conserved internal components. Ideally, LAIV Master Donor Viruses (MDV) should accurately reflect seasonal influenza strains. Unfortunately, the continuous evolution of IBV have led to significant changes in conserved epitopes compared to the IBV MDV based on B/Ann Arbor/1/1966 strain. Here, we propose a recent influenza B/Brisbane/60/2008 as an efficacious MDV alternative, as its internal viral proteins more accurately reflect those of circulating IBV strains. We introduced the mutations responsible for the temperature sensitive (ts), cold adapted (ca) and attenuated (att) phenotype of B/Ann Arbor/1/1966 MDV LAIV into B/Brisbane/60/2008 to generate a new MDV LAIV. In vitro and in vivo analysis demonstrated that the mutations responsible of the ts, ca, and att phenotype of B/Ann Arbor/1/1966 MDV LAIV were able to infer the same phenotype to B/Brisbane/60/2008, demonstrating its potential as a new MDV for the development of LAIV to protect against contemporary IBV strains.

Identification of Two Novel Candidate Genetic Variants Associated With the Responsiveness to Influenza Vaccination.

Background: Annual vaccination is the most effective prevention of influenza infection. Up to now, a series of studies have demonstrated the role of genetic variants in regulating the antibody response to influenza vaccine. However, among the Chinese population, the relationship between genetic factors and the responsiveness to influenza vaccination has not been clarified through genome-wide association study (GWAS). Method: A total of 1,968 healthy volunteers of Chinese descent were recruited and 1,582 of them were available for the subsequent two-stage analysis. In the discovery stage, according to our inclusion criteria, 123 of 1,582 subjects were selected as group 1 and received whole-genome sequencing to identify potential variants and genes. In the verification stage, 29 candidate variants identified by GWAS were selected for further validation in 481 subjects in group 2. Besides, we also analyzed nine variants from previously published reports in our study. Results: Multivariate logistic regression analysis showed that compared with the TT genotype of ZBTB46 rs2281929, the TC + CC genotype was associated with a lower risk of low responsiveness to influenza vaccination adjusted for gender and age (Group 2: P = 7.75E-05, OR = 0.466, 95%CI = 0.319-0.680; Combined group: P = 1.18E-06, OR = 0.423, 95%CI = 0.299-0.599). In the combined group, IQGAP2 rs2455230 GC + CC genotype was correlated with a lower risk of low responsiveness to influenza vaccination compared with the GG genotype (P = 8.90E-04, OR = 0.535, 95%CI = 0.370-0.774), but the difference was not statistically significant in group 2 (P = 0.008). The antibody fold rises of subjects with ZBTB46 rs2281929 TT genotype against H1N1, H3N2,and B were all significantly lower than that of subjects with TC + CC genotype (P < 0.001). Compared with IQGAP2 rs2455230 GC + CC carriers, GG carriers had lower antibody fold rises to H1N1 (P = 0.001) and B (P = 0.032). The GG genotype of rs2455230 tended to be correlated with lower antibody fold rises (P = 0.096) against H3N2, but the difference was not statistically significant. No correlation was found between nine SNPs from previously published reports and the serological response to influenza vaccine in our study. Conclusion: Our study identified two novel candidate missense variants, ZBTB46 rs2281929 and IQGAP2 rs2455230, were associated with the immune response to influenza vaccination among the Chinese population. Identifying these variants will provide more evidence for future research and improve the individualized influenza vaccination program.

Lineage-specific protection and immune imprinting shape the age distributions of influenza B cases.

How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations.

Do Vaccines Need a Gender Perspective? Influenza Says Yes!

Background: Sex differences in immune responses are well known. However, the humoral response in males and females in the case of influenza vaccination is yet to be characterized since studies have shown uneven results. Methods: A retrospective study was conducted in 2,243 individuals (46.9% males) divided by age (15-64 and ≥65 years old). A serological analysis was performed by hemagglutination inhibition assay (HI) just before and 28 days after annual vaccination against seasonal influenza viruses in people vaccinated during the 2006-2018 seasons. A comparison of the humoral responses against influenza A and B viruses contained in the vaccine, between male and female individuals in young adults and elderly was conducted. Results: Significative higher humoral response against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B/Victoria lineage in terms of seroconversion rate were found in elderly women. No significant differences were found in the case of A(H3N2) subtype. Conclusions: Elderly women seem to display a greater humoral response against classical A(H1N1), pandemic A(H1N1)pmd09 and B/Victoria lineage than elderly men. Sex dimorphism does not affect young adults.

Evaluating an app-guided self-test for influenza: lessons learned for improving the feasibility of study designs to evaluate self-tests for respiratory viruses.

BACKGROUND: Seasonal influenza leads to significant morbidity and mortality. Rapid self-tests could improve access to influenza testing in community settings. We aimed to evaluate the diagnostic accuracy of a mobile app-guided influenza rapid self-test for adults with influenza like illness (ILI), and identify optimal methods for conducting accuracy studies for home-based assays for influenza and other respiratory viruses. METHODS: This cross-sectional study recruited adults who self-reported ILI online. Participants downloaded a mobile app, which guided them through two low nasal swab self-samples. Participants tested the index swab using a lateral flow assay. Test accuracy results were compared to the reference swab tested in a research laboratory for influenza A/B using a molecular assay. RESULTS: Analysis included 739 participants, 80% were 25-64 years of age, 79% female, and 73% white. Influenza positivity was 5.9% based on the laboratory reference test. Of those who started their test, 92% reported a self-test result. The sensitivity and specificity of participants' interpretation of the test result compared to the laboratory reference standard were 14% (95%CI 5-28%) and 90% (95%CI 87-92%), respectively. CONCLUSIONS: A mobile app facilitated study procedures to determine the accuracy of a home based test for influenza, however, test sensitivity was low. Recruiting individuals outside clinical settings who self-report ILI symptoms may lead to lower rates of influenza and/or less severe disease. Earlier identification of study subjects within 48 h of symptom onset through inclusion criteria and rapid shipping of tests or pre-positioning tests is needed to allow self-testing earlier in the course of illness, when viral load is higher.