Influenza Vaccine Effectiveness: Defining the H3N2 Problem

2019 ◽  
Vol 69 (10) ◽  
pp. 1817-1823 ◽  
Author(s):  
Edward A Belongia ◽  
Huong Q McLean
Keyword(s):  
Influenza Vaccine ◽  
Observational Studies ◽  
Immune Escape ◽  
Neutralizing Antibody ◽  
Vaccine Effectiveness ◽  
Type B ◽  
Contributing Factors ◽  
Antigenic Sites ◽  
Technology Platforms ◽  
Antigenic Evolution

Abstract Observational studies have consistently shown that influenza vaccine effectiveness (VE) is lower for H3N2 relative to H1N1pdm09 and type B, and this is not entirely explained by antigenic match. The triad of virus, vaccine, and host immunity provides a framework to examine contributing factors. Antigenic evolution facilitates H3N2 immune escape, and increasing glycosylation of the hemagglutinin shields antigenic sites from antibody binding. Egg passage adaptation of vaccine viruses generates mutations that alter glycosylation, impair the neutralizing antibody response, and reduce VE. Complex host immune factors may also influence H3N2 VE, including early childhood imprinting and repeated vaccination, but their role is uncertain. Of the triad of contributing factors, only changes to the vaccine are readily achievable. However, it is unclear whether current licensed non–egg-based vaccines generate superior protection against H3N2. The optimal strategy remains to be defined, but newer vaccine technology platforms offer great potential.

scholarly journals Influenza Vaccine Effectiveness in Preventing Severe Outcomes in Patients Hospitalized with Laboratory-Confirmed Influenza during the 2017–2018 Season. A Retrospective Cohort Study in Catalonia (Spain)

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1465
Author(s):  
Lesly Acosta ◽  
Nuria Soldevila ◽  
Nuria Torner ◽  
Ana Martínez ◽  
Xavier Ayneto ◽  
...  
Keyword(s):  
Cohort Study ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Vaccine Effectiveness ◽  
Public Hospitals ◽  
Categorical Variables ◽  
Type B ◽  
Icu Admission

Seasonal influenza is a common cause of hospital admission, especially in older people and those with comorbidities. The objective of this study was to determine influenza vaccine effectiveness (VE) in preventing intensive care admissions and shortening the length of stay (LOS) in hospitalized laboratory-confirmed influenza cases (HLCI) in Catalonia (Spain). A retrospective cohort study was carried out during the 2017–2018 season in HLCI aged ≥18 years from 14 public hospitals. Differences in means and proportions were assessed using a t-test or a chi-square test as necessary and the differences were quantified using standardized effect measures: Cohen’s d for quantitative and Cohen’s w for categorical variables. Adjusted influenza vaccine effectiveness in preventing severity was estimated by multivariate logistic regression where the adjusted VE = (1 − adjusted odds ratio) · 100%; adjustment was also made using the propensity score. We analyzed 1414 HLCI aged ≥18 years; 465 (33%) were vaccinated, of whom 437 (94%) were aged ≥60 years, 269 (57.8%) were male and 295 (63.4%) were positive for influenza type B. ICU admission was required in 214 (15.1%) cases. There were 141/1118 (12.6%) ICU admissions in patients aged ≥60 years and 73/296 (24.7%) in those aged <60 years (p < 0.001). The mean LOS and ICU LOS did not differ significantly between vaccinated and unvaccinated patients. There were 52/465 (11.2%) ICU admissions in vaccinated cases vs. 162/949 (17.1%) in unvaccinated cases. Patients admitted to the ICU had a longer hospital LOS (mean: 22.4 [SD 20.3] days) than those who were not (mean: 11.1 [SD 14.4] days); p < 0.001. Overall, vaccination was associated with a lower risk of ICU admission. Taking virus types A and B together, the estimated adjusted VE in preventing ICU admission was 31% (95% CI 1–52; p = 0.04). When stratified by viral type, the aVE was 40% for type A (95% CI -11–68; p = 0.09) and 25% for type B (95% CI -18–52; p = 0.21). Annual influenza vaccination may prevent ICU admission in cases of HLCI. A non-significantly shorter mean hospital stay was observed in vaccinated cases. Our results support the need to increase vaccination uptake and public perception of the benefits of influenza vaccination in groups at a higher risk of hospitalization and severe outcomes.

scholarly journals Effectiveness of 2 Influenza Vaccines in Nationwide Cohorts of Finnish 2-Year-Old Children in the Seasons 2015–2016 Through 2017–2018

2020 ◽  
Vol 71 (8) ◽  
pp. e255-e261
Author(s):  
Ulrike Baum ◽  
Sangita Kulathinal ◽  
Kari Auranen ◽  
Hanna Nohynek
Keyword(s):  
Influenza Vaccine ◽  
Virus Type ◽  
Real Life ◽  
Vaccine Effectiveness ◽  
Influenza Vaccines ◽  
Type B ◽  
Live Attenuated Influenza Vaccine ◽  
Vaccine Type ◽  
Decision Making Processes ◽  
Study Population

Abstract Background From 2015–2016 through 2017–2018, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in 2-year-olds was estimated for all 3 seasons. Methods Each season, a nationwide register-based cohort study was conducted. The study population comprised 60 088, 60 860, and 60 345 children in 2015–2016, 2016–2017, and 2017–2018, respectively. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. Results From 2015–2016 through 2017–2018, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2–69.0%), 20.3% (−12.7%, 43.6%), and 30.5% (10.9–45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9–89.8%), 24.5% (−29.8%, 56.1%), and −20.1% (−61.5%, 10.7%). Neither influenza vaccine clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. Conclusions To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates also expressing overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

scholarly journals Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chunyan Yi ◽  
Xiaoyu Sun ◽  
Yixiao Lin ◽  
Chenjian Gu ◽  
Longfei Ding ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Early Stage ◽  
Neutralizing Antibody ◽  
Additive Effect ◽  
Escape Mutation ◽  
Prospective Surveillance ◽  
Antibody Recognition ◽  
Antigenic Sites ◽  
The Impact

Abstract Background The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. Methods Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. Results Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. Conclusions Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.

scholarly journals Further Evidence for Bias in Observational Studies of Influenza Vaccine Effectiveness: The 2009 Influenza A(H1N1) Pandemic

2013 ◽  
Vol 178 (8) ◽  
pp. 1327-1336 ◽  
Author(s):  
M. L. Jackson ◽  
O. Yu ◽  
J. C. Nelson ◽  
A. Naleway ◽  
E. A. Belongia ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Observational Studies ◽  
Influenza A ◽  
Vaccine Effectiveness ◽  
H1n1 Pandemic ◽  
Influenza A H1n1

scholarly journals A Dynamic Model for Evaluation of the Bias of Influenza Vaccine Effectiveness Estimates From Observational Studies

2018 ◽  
Vol 188 (2) ◽  
pp. 451-460 ◽  
Author(s):  
Kylie E C Ainslie ◽  
Meng Shi ◽  
Michael Haber ◽  
Walter A Orenstein
Keyword(s):  
Influenza Vaccine ◽  
Dynamic Model ◽  
Observational Studies ◽  
Vaccine Effectiveness

scholarly journals Neutralization of the emerging SARS-CoV-2 variant Lambda by antibodies elicited by inactivated virus and mRNA vaccines

2021 ◽  
Author(s):  
Mónica Acevedo ◽  
Luis Alonso-Palomares ◽  
Marco Montes de Oca ◽  
Andrés Bustamante ◽  
Aldo Gaggero ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Neutralizing Antibody ◽  
Neutralization Capacity ◽  
Antigenic Sites ◽  
Antibody Titers ◽  
Different Levels

Abstract Here, we used pseudotyped viruses to characterize the neutralization capacity of antibodies elicited by the CoronaVac and BNT162b2 vaccines against the emerging variant of interest Lambda. We observed that BNT162b2 elicits higher neutralizing antibody titers than CoronaVac, ranging from 5.8-fold for the ancestral spike to 9.4-fold for the Lambda variant. Neutralization against D614G, Alpha, Gamma, and Lambda variants was reduced between 1.78 to 3.05-fold for CoronaVac and 1.10 to 1.87-fold for BNT162b2. Structural analyses of the Lambda spike show significant changes in antigenic sites including the 246–252 deletion in an antigenic supersite at the NTD loop and, L452Q/F490S within the RBD that may account for immune escape. Our analysis of pseudotyped viruses also suggests increased infectivity driven by the Lambda spike. Together, our data indicate that inactivated virus and mRNA vaccines elicit different levels of neutralizing antibodies with different potency to neutralize SARS-CoV-2 variants, including the emergent variant Lambda.

scholarly journals Estimates of reduced vaccine effectiveness against hospitalization, infection, transmission and symptomatic disease of a new SARS-CoV-2 variant, Omicron (B.1.1.529), using neutralizing antibody titers

2021 ◽  
Author(s):  
Billy J Gardner ◽  
A. Marm Kilpatrick
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Vaccine Effectiveness ◽  
Vaccine Protection ◽  
Infection Transmission ◽  
Symptomatic Disease ◽  
Antibody Titers ◽  
Protection Against Infection

The emergence of the Omicron variant (B.1.1.529) of SARS-CoV-2 has raised concerns about how mutations in the spike protein might influence immune escape and vaccine protection against infection and disease, COVID-19. Initial estimates of immune escape measure neutralizing antibody titers, which have been shown to be a correlate of protection for COVID-19, but vary among studies. However, no studies have examined variation in vaccine effectiveness (VE) using estimated reductions in neutralizing antibody titers across virus variants. We quantified consistency in relative neutralizing antibody titers across studies. We then examined relationships between variant-specific reductions in neutralizing antibodies and protection against documented infection, symptomatic disease, and hospitalizations across variants and vaccines. We found considerable variation in variant-specific neutralizing antibody titers between studies, but within-study comparisons across variants were far more robust. There was insufficient data to estimate VE for a single vaccine across variants, especially for higher levels of immune evasion (>7-fold reductions in neutralizing antibody titers) observed with the Omicron variant (40-fold). Instead, we leveraged variation among both vaccines and virus variants to estimate VE - neutralizing antibody titer relationships across a 30 to 100-fold range of neutralizing antibody titers reduction. Omicron increased the risk of hospitalization four to five-fold and increased the risk of symptomatic disease seven to ten-fold for mRNA vaccinees, with similar relative effects for recently vaccinated, or individuals with waned antibody titers. Third doses restored titers and protection to levels similar to waned immunity against Delta. Overall, these analyses indicate that vaccine effectiveness against severe disease is significantly diminished for waned individuals, and protection against infection, symptomatic disease and transmission is nearly eliminated. However, third doses significantly ameliorate these reductions but only restore protection to levels equivalent to waned protection against the Delta variant. The invasion of Omicron is likely to result in widespread infection, and substantial hospitalizations unless widespread boosting of immunity occurs.

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