Seasonal Influenza Research Articles

Estimated Burden of Influenza and Direct and Indirect Benefits of Influenza Vaccination

ImportanceVaccination is the safest and most effective way to prevent infectious diseases. It not only reduces disease in the vaccinated portion of a population but also potentially provides indirect benefit to the unvaccinated portion. Indirect benefits to the unvaccinated portion in a population are difficult to estimate since indirect benefits cannot be determined from the general population simply.ObjectiveTo estimate the influenza case burden, both direct and indirect, averted by vaccination using an agent-based model, which models agents as individuals in the simulation population.Design, Setting, and ParticipantsIn this decision analytical modeling study, simulations included varied levels of virus transmissibility, vaccine effectiveness, and vaccine uptake among the 2010 Allegheny County, Pennsylvania, census population. Simulations were run from August 15, 2022, to May 31, 2023. Individuals were vaccinated beginning in September of the simulation year.ExposureInfluenza infection.Main Outcomes and MeasuresDifferences between number of influenza cases in vaccinated and unvaccinated portions of the population.ResultsThe population used in this study consisted of 1 218 695 agents (median [IQR] age, 40.6 [3.6-77.6] years; 51% female) and was statistically similar in demographics to the 2010 Allegheny County census population. The mean (SD) burden of influenza averted by vaccination with a vaccine effectiveness of 40% ranged from 32.9% (0.9%) in the high transmission scenario to 41.5% (3.4%) in the low transmission scenario for seasonal influenza. In the model, indirect benefit to the unvaccinated portion of the population was found over a range of modeled transmissibility characteristics of seasonal influenza and varied levels of vaccine effectiveness and vaccination coverage; however, direct benefit to the vaccinated portion was greater in all scenarios. At the highest levels of transmissibility, such as might be found in pandemic influenza, indirect benefit decreased and eventually disappeared.Conclusions and RelevanceIn this analytical model study, influenza vaccination provided substantial benefit in reducing infections to both the vaccinated and unvaccinated portions of the population. Even when both vaccine effectiveness and vaccine uptake were low, vaccination showed marked reductions in disease burden for transmission levels characteristic of seasonal influenza. However, when the level of transmission was very high, even a highly effective vaccine did not protect unvaccinated individuals. These findings underscore the importance of vaccination in disease prevention and control and show that indirect benefits are limited in high transmission situations.

Medical Comorbidities as the Independent Risk Factors of Severe Adenovirus Respiratory Tract Infection in Adults

Adenovirus is an important respiratory virus that causes severe diseases in immunocompromised patients. Data on its impact in immunocompetent patients are relatively limited. We conducted a territory-wide retrospective study on adult patients hospitalized for respiratory tract infections caused by adenovirus or influenza viruses in Hong Kong between 1 January 2016 and 30 June 2023. Inpatient mortality, severe respiratory failure (SRF), secondary bacterial pneumonia and acute kidney injury (AKI) were compared. The risk factors for these outcomes in patients hospitalized for adenovirus respiratory tract infections were assessed. Overall, 41,206 and 528 patients were hospitalized for influenza and adenovirus respiratory tract infections, respectively. Patients with respiratory tract infections due to adenoviruses showed significantly higher risk of inpatient mortality, SRF, secondary bacterial pneumonia and AKI compared to seasonal influenza. Medical comorbidities including cardio-pulmonary diseases, end-stage kidney disease requiring dialysis, and a lower estimated glomerular filtration rate were robust independent risk factors for inpatient mortality and serious respiratory outcomes in adenovirus respiratory tract infections. Adults hospitalized for adenoviruses respiratory tract infections had a significantly higher risk of inpatient mortality and adverse outcomes than adults infected with seasonal influenza. Medical comorbidities are important risk factors for severe adenovirus infections in adult patients.

Development of DNA and mRNA-LNP vaccines against an H5N1 clade 2.3.4.4b influenza virus

ABSTRACT Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States. While nucleic acid-based vaccines such as mRNA-lipid nanoparticles (LNPs) have several potential advantages during a viral epidemic compared to traditional seasonal influenza vaccines, their utility and efficacy against H5N1 viruses remain incompletely defined. Here, we developed novel DNA- and mRNA-LNP-based vaccines encoding both hemagglutinin (HA) and neuraminidase (NA) proteins from the human-isolated highly pathogenic avian influenza H5N1 strain, A/Texas/37/2024, in a single open reading frame. This dual-antigen expression approach elicited strong protective immune responses targeting both the HA and NA proteins and provided complete protection against lethal viral challenges in a murine model. The pre-clinical data described in this work suggest that these multi-valent, adaptable, and scalable vaccine approaches may represent practical and rapid solutions to mediate robust protection from emerging zoonotic influenza virus threats. IMPORTANCE Vaccines capable of protecting from infection with the H5N1 influenza viruses actively circulating in dairy cattle could be deployed to protect livestock and potentially also be used to protect human health. Here, we describe the development of protective DNA and mRNA-lipid nanoparticle vaccines targeting hemagglutinin and neuraminidase proteins from the highly pathogenic avian influenza (HPAI) H5N1 A/Texas/37/2024 virus and show that they are both protective against severe morbidity and mortality in a mouse model. Thus, the vaccines described in this work represent effective approaches to limit the current circulation of H5N1 viruses in animals and may represent practical solutions for human vaccination in the event of sustained human transmission of HPAI H5N1 viruses.

Cases, Hospitalization, and Mortality in COVID-19 and Influenza Among Veterans in 2022-2025 Influenza Seasons.

This cohort study examines rates of positive tests, hospitalizations, and deaths for COVID-19 and influenza across the influenza seasons of 2022 to 2023, 2023 to 2024, and 2024 to 2025 among US veterans.

The optimal strategy for seasonal influenza vaccination to prevent high-intensity level of influenza epidemics in Zhejiang, China: an integrated transmission-dynamic and health-economic modeling analysis

The optimal strategy for seasonal influenza vaccination to prevent high-intensity level of influenza epidemics in Zhejiang, China: an integrated transmission-dynamic and health-economic modeling analysis

Seasonal PM 2.5 exposures induce differential responses to influenza A virus infection in primary human airway epithelial cells.

Background Air pollution, specifically fine particulate matter (PM 2.5 ), in China is responsible for millions of excess deaths each decade. Examinations of Chinese municipalities have revealed correlations between ambient PM 2.5 levels and the prevalence and severity of respiratory viral infections. Seasonal sources of ambient PM 2.5 vary, with coal combustion for indoor heating significantly contributing during colder months. Due to this seasonality, we sought to investigate whether exposure to seasonal PM 2.5 collected in Xinxiang, China would differentially alter the response to subsequent influenza A/California/04/2009 (H1N1) viral infection in a primary human nasal epithelial cell (HNEC) culture model. After the PM 2.5 samples were chemically analyzed, HNECs collected from males (N = 4) and females (N = 3) grown at air-liquid interface were exposed to 22 µg/cm 2 of seasonal PM 2.5 followed by inoculation with influenza A H1N1 at MOI = 0.001. At 2 and 24 h post infection (p.i.) we assessed transcriptional changes and basolateral release of immune and antiviral mediators. Results Summer and fall PM 2.5 samples contained a greater organic carbon mass fraction compared to winter and spring. Winter contained the largest mass fraction of anionic components and spring the largest inorganic element mass fraction. In response to infection alone without PM 2.5 exposure, the transcriptional response to infection at 24 h p.i. differed between the sexes with males having more robust interferon pathway activation. Exposure to the seasonal PM 2.5 samples without infection induced a moderate transcriptional response at 2 h, with the winter PM 2.5 inducing the greatest response. The seasonal PM 2.5 exposures followed by viral infection resulted in a more robust transcriptional response at 2 h p.i. with the winter, spring, and fall PM 2.5 samples (but not the summer PM 2.5 ) upregulating many inflammatory pathways. At 24 h p.i., only the spring PM 2.5 sample increased inflammatory and antiviral mediator proteins in the basolateral medium, while winter PM 2.5 increased these inflammatory markers in the mock infected cultures. Conclusions Chemical differences in seasonal PM 2.5 from the winter, spring, and fall, coinciding with influenza season, likely contribute to the adjuvant pro-inflammatory effects of exposure on antiviral host response. Heightened inflammation early in infection could contribute to worsened pathogenesis.

Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo

The rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000–650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vaccines and therapeutics is critical, the evaluation of these interventions is constrained by the requirement for high biosafety containment facilities. To circumvent these challenges, we developed S-Lux, a replication-deficient, single-cycle recombinant influenza virus expressing firefly luciferase (Flux) as a reporter protein. S-Lux can be pseudotyped with haemagglutinin from avian influenza, H5 and H7, enabling real-time monitoring of viral infection in vivo, and facilitate therapeutic antibody evaluation in low-containment facilities. In mice, S-Lux infection resulted in dose-dependent bioluminescent expression in the mouse airways and allowed evaluation of neutralising monoclonal antibodies and clearance of infected cells in mice. To extend this system, we generated ES-Lux by pseudotyping with the Ebola Glycoprotein (GP) and demonstrated that ES-Lux can be used to evaluate the efficacy of Ebola GP-targeting antibodies in vivo. Together, S-Lux and ES-Lux enable robust, simple and time-efficient assessment of antiviral therapy targeting influenza and Ebola virus in vivo, overcoming biosafety constraints that limit traditional efficacy studies.

What may influence older Europeans' decision about the seasonal influenza vaccine? A literature review of socio-cultural and psycho-social factors related to seasonal influenza vaccination uptake.

What may influence older Europeans' decision about the seasonal influenza vaccine? A literature review of socio-cultural and psycho-social factors related to seasonal influenza vaccination uptake.

Seasonal influenza vaccination uptake among health and medical college students: A discrete choice experiment

ABSTRACT Seasonal influenza is a highly contagious virus posing significant health risks, especially to children, pregnant women, and older adults. Despite its crucial role in prevention and reducing severity, vaccination rates among medical and health students, who frequently interact with vulnerable groups, remain low. This study investigates attributes of influenza vaccines that predict vaccination decisions within this population, while also examining how these preferences vary based on the health literacy levels of the respondents. Between May and June 2024, 239 Slovenian medical and health students completed an online discrete choice experiment presenting vaccines varying in efficacy, side effects, and administration site. Preferences were analyzed to identify key attributes. Results showed that higher efficacy and fewer side effects drove vaccine choice across all disciplines. Medical students favored faculty-based vaccination, whereas nursing and other health discipline students preferred GP offices and NIPH units. Health literacy did not alter the importance of efficacy and safety, but those with sufficient literacy showed a stronger preference for GP settings over faculty sites. Campaigns should emphasize vaccine efficacy and the low risk of severe side effects, reassuring that mild reactions are transient. Facilitating GP-based vaccination for nursing and other health discipline students may further improve uptake.

Adenovirus and mRNA vaccines as well as mucosal boosting improve protective efficacy against influenza virus challenge in macaques.

The clinically approved seasonal influenza vaccines provide only 10 to 60% efficacy, necessitating strategies to improve vaccine performance. Here, we explored strategies for improving influenza vaccine efficacy using gene-based vaccines and mucosal boosting strategies in nonhuman primates. All vaccinated cynomolgus macaques were primed with the clinical quadrivalent inactivated virus (QIV) vaccine. We evaluated a rhesus adenovirus (RhAd52) vector delivered by intramuscular or mucosal routes and an mRNA vaccine encoding the hemagglutinin of A/H1N1/Wisconsin/67/2022 delivered intramuscularly as boosts compared with the QIV vaccine delivered intramuscularly and the quadrivalent live-attenuated influenza virus (LAIV) vaccine delivered intranasally. Boosting with RhAd52 and mRNA vaccines induced more robust humoral and cellular immune responses than the clinically approved vaccines and provided improved protective efficacy against a high-dose homologous challenge with A/H1N1/Wisconsin/67/2022. The RhAd52 vaccine delivered by the intratracheal route elicited robust mucosal antibody and T cell responses and provided optimal protection in the upper and lower respiratory tracts. Both peripheral and mucosal antibody responses, as well as mucosal T cell responses, correlated with protection against viral loads. Altogether, this study defines strategies for improving H1N1 seasonal influenza vaccine efficacy by using gene-based vaccines and by optimizing mucosal immunity.

Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccine uptake among pregnant women (EPIC study) in Australia.

Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccine uptake among pregnant women (EPIC study) in Australia.

Impact of SARS-CoV-2 vaccinations on pandemic dynamics: Trends in cases, deaths, and fatality risks

Despite the decrease in COVID-19 testing and reporting new infections, the numbers of new cases and deaths per capita registered in some European countries and USA in September 2024 were higher than endemic limits and exceeded seasonal flu mortality. These facts make the development of new vaccines or the further use of existing ones very urgent. The averaged daily numbers of cases DCC and death DDC per million, case fatality risks CFR=DDC/DCC in 2020-2024 calculated for 34 countries and regions were used to investigate the trends versus vaccination levels. These trends together with the published before results of statistical analysis show that existing vaccines cannot reduce the number of new COVID-19 cases and deaths, i.e. vaccinations reduced severity but not transmission. Therefore, it is still necessary to avoid close contacts and crowded places, trace and isolate infected people, wear masks in transport and medical facilities, wash hands more often, etc. Nevertheless, vaccinations and boosters can be recommended in order to reduce the severity of SARS-CoV-2 disease and probability of dying for infected individuals (CFR). Recent epidemic waves can probably be controlled with the use of the immediate and sufficient increase of the number of tests.

Dynamic adaptation mutations and pathogenic characterization of a mouse-adapted seasonal human H3N2 influenza virus

BackgroundH3N2 influenza A viruses [A(H3N2)] circulate as seasonal influenza in humans worldwide, resulting in a huge disease burden. Adaptation study of A(H3N2) in mice could provide a basis for preclinical evaluation of antivirals and vaccines targeting A(H3N2) and identify the genetic markers responsible for the viral adaptation, replication, and pathogenesis.MethodsLung-to-lung passaging of wild-type (WT) A(H3N2) strain was performed in C57BL/6J mice. Amino acid (AA) mutations occurred during the passaging and temporal dynamics of these mutations were identified using the next-generation sequencing. We determined the polymerase activity of the ribonucleoprotein (RNP) complex containing mutation genes and compared the pathogenicity between the mouse-adapted (MA) and A(H3N2)-WT strains based on body weight change, survival rate, lung index, lung viral load, and lung pathology of the infected mice.ResultsThe A(H3N2)-MA strain was obtained after seventeen lung-to-lung passages in mice. 14 AA mutations in the PB2, PB1, PA, HA, NP, and M1 genes were identified in the A(H3N2)-MA strain compared to the A(H3N2)-WT strain. In addition, the polymerase activity of the RNP complex containing mutation genes was increased, and the pathogenicity of the MA virus is significantly higher than that of the WT strain.ConclusionsOne A(H3N2)-MA strain has been developed that can infect and kill mice. The MA strain showed stronger replication ability and pathogenicity than the A(H3N2)-WT strain. This A(H3N2)-MA model provides a valuable basis for evaluating the effects of drugs and vaccines and for studying pathogenesis.

COVID-19: A Comprehensive Review of Epidemiology, Pathogenesis, And Clinical Management

By 2024, COVID-19 had mostly become an endemic virus, and like seasonal flu, its control is now integrated into routine public health monitoring. Although the severity has decreased due to vaccination, booster shots, and better treatments, WHO and CDC are keeping a careful eye on the emergence of novel Omicron-derived variants (such as JN.1, XEC, and NB.1.8.1/Nimbus). About 6–7% of individuals worldwide suffer with long-term COVID, which is still a serious problem. Its symptoms include exhaustion, mental fog, and dyspnoea, and it disproportionately affects women, those with disabilities, and those with lower incomes. In terms of the economy, the pandemic revealed disparities in health and vaccination availability while speeding up digital transformation, remote labour, and supply-chain shifts. Despite ongoing global efforts in pandemic preparedness, future health disasters are always a possibility

Increasing the uptake of Live Attenuated Influenza Vaccine through a new school-based vaccination programme in Ireland.

Increasing the uptake of Live Attenuated Influenza Vaccine through a new school-based vaccination programme in Ireland.

Uptake, knowledge, attitudes, and practices toward seasonal influenza vaccination among community healthcare workers during the COVID-19 pandemic in Chongqing Municipality, China: A cross-sectional study

BackgroundSeasonal influenza is significantly associated with high morbidity and mortality. Vaccination of healthcare workers (HCWs), who represent a high-risk group, is a crucial preventive measure to reduce the spread of outbreaks and the severity of disease. Therefore, the aim of this study was to evaluate the levels of influenza vaccine acceptance and uptake, as well as the determinants influencing these factors among HCWs in Chongqing, China.MethodsWe conducted a cross-sectional survey among community HCWs aged ≥ 22 years from July 15, 2021 to September 30, 2021. An anonymous self-administered questionnaire was used to assess the knowledge and key factors of HCWs regarding vaccination acceptance and recommendation to patients. Parametric and nonparametric statistical analyses were performed with the use of the Statistical Program for the Social Sciences (SPSS) version 25.0.ResultThe coverage rate for the seasonal influenza vaccination in Chongqing HCWs was 46.2% in the 2020–2021 seasons. HCWs who were females (OR: 2.10 95% CI: 1.54–2.85), had influenza experience (OR:1.98 95% 1.27–3.11), without influenza vaccination hesitancy (IVH) (OR:2.10 95% 1.58–2.79), and/or in a vaccination-promoted community (OR:6.50 95% 3.99–10.60) would be more likely to be vaccinated. HCWs who were vaccinated in 2020–2021 (OR: 8.48 95% 6.03–11.93), without IVH (OR: 4.15 95% 2.91–5.90), and/or in a vaccination-promoted community (OR: 2.08 95%1.37–3.16) would be more willing to be vaccinated. HCWs who were with knowledge scores ≥ 4 (OR: 2.58 95% 1.30–5.13), without IVH (OR: 2.33 95% 1.05–5.13), were in a vaccination-promoted community (OR: 2.65 95% 1.51–4.65), and/or with vaccination willingness (OR: 4.32 95% 2.16–8.64) would be more likely to recommend vaccination to patients.ConclusionThe influenza vaccination rate among Chongqing HCWs increased in the 2020–2021 season but remained relatively low. It is critical to improve knowledge of influenza and its vaccine among HCWs, implement activities to moderate their IVH and expand the free vaccination policy, and interventional measures aiming to promote influenza vaccination.

Effectiveness of pay it forward intervention compared to free and user-paid vaccinations on seasonal influenza vaccination among older adults across seven cities in China: study protocol of a three-arm cluster randomized controlled trial

BackgroundSeasonal influenza poses an enormous burden worldwide, with older adults facing preventable morbidity and mortality. However, seasonal influenza vaccination coverage is poor among older populations in China. Pay-it-forward (giving a person a free vaccine and an opportunity to donate to support others) and financial incentives (e.g. free vaccination) could be effective in improving influenza vaccine uptake, but there are no prospective comparisons of these two strategies among older adults. The proposed study aims to compare the effectiveness of the pay-it-forward strategy in increasing influenza vaccination against free vaccination and user-paid vaccination among older adults in China.MethodsThis study is a three-arm cluster randomized controlled trial, which will be conducted in 21 community health centers across seven cities in China. A total of 1113 eligible older adults aged ≥ 60 years will be recruited. Three clusters in each city (total of 21 clusters in 7 cities) will be randomized into three arms in a 1:1:1 ratio, including (1) pay-it-forward arm: free vaccination and participants donate any amount of money to help other people; (2) free vaccination arm; and (3) standard-of-care arm (user-paid vaccination). The primary outcome is influenza vaccination verified by administrative records. Secondary outcomes include willingness to be vaccinated, willingness to donate, amount of donation, and incremental cost-effectiveness ratio. The primary outcome will be calculated for each arm and compared using one-way variance analysis.DiscussionThis study will examine the effectiveness of pay-it-forward strategy in comparison to the free vaccination and user-paid vaccination in improving influenza vaccination among older adults. Our findings will provide insights into better strategies for enhancing influenza vaccination, and support evidence-based policy decisions for promoting influenza vaccination.Trial registrationChinese Clinical Trial Registry (No. ChiCTR2400086840). Registered on 11 July 2024.

Incidence of acute respiratory infections and their associated pathogen distribution among residents in Shanghai, China: Preliminary results from community-based surveillance in the 2023-24 influenza season.

Incidence of acute respiratory infections and their associated pathogen distribution among residents in Shanghai, China: Preliminary results from community-based surveillance in the 2023-24 influenza season.

Navigating the crossroads of health and wealth: socioeconomic inequality in flu vaccination uptake among the elderly in Iran

BackgroundThere is limited evidence regarding socioeconomic-related inequalities in flu vaccination uptake among the elderly in developing countries like Iran. This study aims to examine these inequalities and identify the main determinants of observed inequalities among the elderly in Iran.MethodIn this cross-sectional study, we collected data on sociodemographic factors, economic status, flu vaccination history, and reasons for receiving or declining the vaccine among 1,192 individuals aged 60 years and older through multistage sampling in 2024. Monthly household expenditures were used as a proxy to measure the economic status of the participants’ households. We initially employed multiple logistic regression to assess the main factors affecting flu vaccination uptake among the samples. Subsequently, we utilized the concentration curve (CC) and concentration index (CI), specifically Wagstaff normalized CI and Erreygers normalized CI, to illustrate and quantify socioeconomic inequalities in flu vaccination uptake. Additionally, decomposition analysis was conducted to identify primary determinants of economic-related inequality in flu vaccination.ResultsThis study found that the prevalence of flu vaccination uptake among the elderly was 29.69% (n = 354) for the current or previous flu season and 40.81% (n = 486) for having ever received a flu vaccination at any time in their lives. Key factors influencing vaccination included education level, monthly household expenditures, consultations with health professionals, trust in healthcare providers, and prior vaccination history. Both Wagstaff normalized CI and Erreygers normalized CI indicated that vaccination distribution was disproportionately concentrated among wealthier groups. Decomposition analysis revealed that flu vaccination history (101.1%), household costs (21.3%), consultations regarding flu vaccination from health centers or professionals (13.6%), trust in health professionals concerning flu vaccination (12.4%), and education level (7.9%). were significant determinants of observed inequalities.ConclusionThis study highlights significant socioeconomic inequalities in flu vaccination uptake among the elderly in Iran, indicating that wealthier individuals are more likely to receive vaccinations. Addressing these disparities through targeted interventions is essential for improving vaccination rates and overall public health outcomes among vulnerable populations.

Different antigenic distance metrics generate similar predictions of influenza vaccine response breadth despite moderate correlation.

Influenza continuously evolves to escape population immunity, which makes formulating a vaccine challenging. Antigenic differences between vaccine strains and circulating strains can affect vaccine effectiveness (VE). Quantifying the antigenic difference between vaccine strains and circulating strains can aid interpretation of VE, and several antigenic distance metrics have been discussed in the literature. Here, we compare how the predicted breadth of vaccine-induced antibody response varies when different metrics are used to calculate antigenic distance. We analyzed data from a seasonal influenza vaccine cohort which collected serum samples from 2013/14 - 2017/18 at three study sites. The data include pre- and post-vaccination HAI titers to the vaccine strains and a panel of heterologous strains. We used that data to calculate four different antigenic distance measures between assay strains and vaccine strains: difference in year of isolation (temporal), p -Epitope (sequence), Grantham's distance (biophysical), and antigenic cartography distance (serological). We analyzed agreement between the four metrics using Spearman's correlation and intraclass correlation. We then fit Bayesian generalized additive mixed-effects models to predict the effect of antigenic distance on post-vaccination titer after controlling for confounders and analyzed the pairwise difference in predictions between metrics. The four antigenic distance metrics had low or moderate correlation for influenza subtypes A(H1N1), B/Victoria, and B/Yamagata. A(H3N2) distances were highly correlated. We found that after accounting for pre-vaccination titer, study site, and repeated measurements across individuals, the predicted post-vaccination titers conditional on antigenic distance and subtype were nearly identical across antigenic distance metrics, with A(H1N1) showing the only notable deviation between metrics. Despite moderate correlation among metrics, we found that different antigenic distance metrics generated similar predictions about breadth of vaccine response. Costly titer assays for antigenic cartography may not be needed when simpler sequence-based metrics suffice for quantifying vaccine breadth.