Influenza Vaccine Effectiveness: New Insights and Challenges

Abstract

Methods for assessing influenza vaccine efficacy and effectiveness have evolved over six decades. Randomized trials remain the gold standard for licensure, but observational studies are needed for annual assessment of vaccine effectiveness (VE). The test-negative design (TND) has become the de facto standard for these field studies. Patients who seek medical care with acute respiratory illness are tested for influenza, and VE is estimated from the odds of vaccination among influenza cases versus test-negative controls. VE varies across seasons, populations, age groups, and products, but VE estimates are consistently higher for A(H1N1) pdm09 and type B compared with A(H3N2). VE studies are increasingly used in combination with molecular epidemiology to understand the viral and immune system factors that drive clinical efficacy and effectiveness. The emerging field of immunoepidemiology offers the potential to understand complex host-virus interactions that affect vaccine protection, and this knowledge will contribute to universal vaccine development.

Vaccine-elicitation of cross-group neutralizing protective antibodies to influenza A viruses

“…Supplementary Fig. 1-9 Supplementary table [1][2][3][4][5][6][7] 105 and is also made available for use under a CC0 license.…”

“…Moreover, it poses a unique biological challenge by evading host immune responses through its genetic plasticity leading to antigenic variation, making the virus a constantly moving target. Current influenza vaccines provide narrow-spectrum protection against antigenically closely matched strains, resulting in inconsistent 10-60% vaccine efficacy against symptomatic disease in humans 1 . This also necessitates annual update of the vaccine strains in order to match the predicted circulating viruses.…”

MADE: A Computational Tool for Predicting Vaccine Effectiveness for the Influenza A(H3N2) Virus Adapted to Embryonated Eggs

“…Even though many efforts including a universal influenza vaccine [30], non-egg cell lines [31,32], genetically engineered viruses with egg-adapted neuraminidase (NA) [33,34] and DNA vaccines [4] have been explored to improve vaccine efficacy, the transition to newer technologies [35] will likely progress rather slowly due to economic and technological limitations. It is likely that the egg-based vaccine production system will continue for quite some time [4,7]. Given the steadily increasing intensity of egg passage adaptation of the H3N2 influenza strains [18], MADE provides a timely and powerful method for the research and public community circumventing the impact of egg passage adaptation when selecting seasonal A/H3N2 influenza vaccine strains.…”

“…There are many factors that can influence influenza vaccine effectiveness (VE) [7,8]. In addition to antigenic drift [2,3], several other factors ranging from glycosylation of the hemagglutinin [9], egg passage adaptation [10], repeated vaccination [11], imprinting and cohort effect [12] as well as the waning effect [13] can contribute to the variability of vaccine efficacies [4].…”

Poor Vaccine Effectiveness against Influenza B-Related Severe Acute Respiratory Infection in a Temperate North Indian State (2019–2020): A Call for Further Data for Possible Vaccines with Closer Match

“…Similarly, there is an interest in development of alternate platforms of vaccine manufacturing so that the turnaround time of manufacturing is faster, which would result in a better match between the circulating and the vaccine strain. In this connection, alternate strategies include using cell-based vaccines, adjuvanted vaccines, recombinant vaccines, high dose vaccines, etc., in order to achieve a closer match between the circulating and the vaccine strain for a better VE and a better immunological response to the administration of the vaccine [45]. mRNA-based influenza vaccine trials are underway currently and have been initiated recently [46].…”