Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines

2021 ◽  
Author(s):  
Nathaniel M Lewis ◽  
Jessie R Chung ◽  
Timothy M Uyeki ◽  
Lisa Grohskopf ◽  
Jill M Ferdinands ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Sample Size ◽  
Virus Type ◽  
Scenario Analysis ◽  
Host Response ◽  
Vaccine Virus ◽  
Influenza Vaccines ◽  
Relative Efficacy ◽  
Clinical Endpoint ◽  
Different Seasons

Abstract Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of two vaccine products. Estimates of rVE for enhanced influenza vaccines (eIV) vs. standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (e.g., all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (i.e., as compared with placebo) on the interpretation of rVE of eIV vs IIV. We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials.

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 An Antigenic Thrift-Based Approach to Influenza Vaccine Design

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 657
Author(s):  
Jai S. Bolton ◽  
Hannah Klim ◽  
Judith Wellens ◽  
Matthew Edmans ◽  
Uri Obolski ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Season ◽  
Vaccine Design ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Immune Protection ◽  
Immune Selection ◽  
Drift Theory ◽  
Gradual Accumulation ◽  
Additional Constraints

The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host’s immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution – antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.

scholarly journals M2e-Based Influenza Vaccines with Nucleoprotein: A Review

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 739
Author(s):  
Mei Peng Tan ◽  
Wen Siang Tan ◽  
Noorjahan Banu Mohamed Alitheen ◽  
Wei Boon Yap
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Matrix Protein ◽  
Severe Disease ◽  
Chimeric Protein ◽  
Influenza Vaccines ◽  
Cell Responses ◽  
Hospitalization Rates ◽  
Humoral Responses ◽  
Universal Influenza Vaccine

Discovery of conserved antigens for universal influenza vaccines warrants solutions to a number of concerns pertinent to the currently licensed influenza vaccines, such as annual reformulation and mismatching with the circulating subtypes. The latter causes low vaccine efficacies, and hence leads to severe disease complications and high hospitalization rates among susceptible and immunocompromised individuals. A universal influenza vaccine ensures cross-protection against all influenza subtypes due to the presence of conserved epitopes that are found in the majority of, if not all, influenza types and subtypes, e.g., influenza matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Despite its relatively low immunogenicity, influenza M2e has been proven to induce humoral responses in human recipients. Influenza NP, on the other hand, promotes remarkable anti-influenza T-cell responses. Additionally, NP subunits are able to assemble into particles which can be further exploited as an adjuvant carrier for M2e peptide. Practically, the T-cell immunodominance of NP can be transferred to M2e when it is fused and expressed as a chimeric protein in heterologous hosts such as Escherichia coli without compromising the antigenicity. Given the ability of NP-M2e fusion protein in inducing cross-protective anti-influenza cell-mediated and humoral immunity, its potential as a universal influenza vaccine is therefore worth further exploration.

scholarly journals Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Santosh Dhakal ◽  
Sabra L. Klein
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Virus Vaccine ◽  
Vaccine Efficacy ◽  
Public Health Problem ◽  
Influenza Virus Vaccine ◽  
Host Factors ◽  
Influenza Vaccines ◽  
Vaccine Type ◽  
Induced Immunity

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

scholarly journals Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults

Vaccine ◽  
2020 ◽  
Vol 38 (2) ◽  
pp. 242-250 ◽  
Author(s):  
Brandon Essink ◽  
Carlos Fierro ◽  
Jeffrey Rosen ◽  
Amparo L. Figueroa ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Influenza Vaccines ◽  
Quadrivalent Influenza Vaccine

scholarly journals A Randomized Trial of Candidate Inactivated Quadrivalent Influenza Vaccine versus Trivalent Influenza Vaccines in Children Aged 3–17 Years

2013 ◽  
Vol 207 (12) ◽  
pp. 1878-1887 ◽  
Author(s):  
Joseph B. Domachowske ◽  
Heidemarie Pankow-Culot ◽  
Milagros Bautista ◽  
Yang Feng ◽  
Carine Claeys ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Randomized Trial ◽  
Influenza Vaccines ◽  
Quadrivalent Influenza Vaccine

scholarly journals Effectiveness of Influenza Vaccines in the HIVE household cohort over 8 years: is there evidence of indirect protection?

2021 ◽  
Author(s):  
Ryan E. Malosh ◽  
Joshua G. Petrie ◽  
Amy Callear ◽  
Rachel Truscon ◽  
Emileigh Johnson ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Vaccine Coverage ◽  
Influenza Virus Infection ◽  
Influenza Vaccines ◽  
Mixed Effect ◽  
Vaccination Programs ◽  
Vaccine Recommendations ◽  
Influenza A H1n1 ◽  
Low Coverage

AbstractBackgroundThe evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (i.e. indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort.MethodsUsing longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households.ResultsThe pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8); and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (−6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccine coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VET was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households.ConclusionInfluenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. While there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.

scholarly journals Start of the influenza season 2008-9 in Europe - increasing influenza activity moving from West to East dominated by A(H3N2)

2009 ◽  
Vol 14 (3) ◽  
Author(s):  
N Goddard ◽  
P Zucs ◽  
B Ciancio ◽  
F Plata ◽  
O Hungnes ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Northern Hemisphere ◽  
Virus Type ◽  
Influenza Season ◽  
Type A ◽  
Neuraminidase Inhibitors ◽  
Influenza Activity

The influenza season 2008-9 started in week 49 of 2008 and is so far characterised by influenza virus type A subtype H3N2. Isolates of this subtype that were tested proved susceptible to neuraminidase inhibitors, but resistant to M2 inhibitors. The circulating A(H3N2) viruses are antigenically similar to the component in the current northern hemisphere influenza vaccine.

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