Different Repeat Annual Influenza Vaccinations Improve the Antibody Response to Drifted Influenza Strains

Abstract

Seasonal influenza vaccine formulas change almost every year yet information about how this affects the antibody repertoire of vaccine recipients is inadequate. New vaccine virus strains are selected, replacing older strains to better match the currently circulating strains. But even while the vaccine is being manufactured the circulating strains can evolve. The ideal response to a seasonal vaccine would maintain antibodies toward existing strains that might continue to circulate, and to generate crossreactive antibodies, particularly towards conserved influenza epitopes, potentially limiting infections caused by newly evolving strains. Here we use the hemagglutination inhibition assay to analyze the antibody repertoire in subjects vaccinated two years in a row with either identical vaccine virus strains or with differing vaccine virus strains. The data indicates that changing the vaccine formulation results in an antibody repertoire that is better able to react with strains emerging after the vaccine virus strains are selected. The effect is observed for both influenza A and B strains in groups of subjects vaccinated in three different seasons. Analyses include stratification by age and sex.Influenza causes widespread seasonal disease and vaccination has been shown to reduce illness among the population [1][2][3][4] . Several studies have demonstrated that vaccination confers protection against virologically confirmed influenza 5 . However, understanding vaccination effectiveness is complicated because a large portion of the population is asymptomatically infected 6 . The circulating strains evolve from season to season leading to changes in vaccine formulation which further complicates comparisons between seasons.Vaccine effectiveness can be measured by controlled clinical trials but comparisons between trials is complicated by factors such as the prevalence of the circulating virus and the closeness of virus match each season 7 . Observational studies, used in places where universal vaccination recommendations make it unethical to perform trials with placebos, are an increasingly common way of measuring vaccine effectiveness among the general population. Test-negative studies are a widely used method but the estimates for vaccine effectiveness vary widely depending on the study design and often have overlapping confidence intervals [8][9][10] . Correlates of protection, such as the hemagglutination inhibition (HI) titer, are widely used to assess vaccine efficacy. HI titers are associated with reduced risk of disease but there is significant variation in the protective titer depending on factors such as the age of the recipient and the severity of the influenza season [11][12][13] . It has also been reported that factors not detected in HI assays are associated with reduced risk of infection 14,15 .Changes in the annual vaccine formulation are compelled by the antigenic drift associated with seasonal influenza viruses. Despite the best efforts of a group of experts in selecting the candidate vaccine virus (CV...

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

“…In the face of the vast antigenic diversity of IAV, not only in swine but also in humans and avian species, efforts have been focused on exploring mechanisms to potentiate immune responses to vaccine antigens to induce broader protection. Some approaches include testing different adjuvants to target specific pathways of the immune response (40)(41)(42), and others have examined various prime-boost strategies (43)(44)(45)(46)(47)(48)(49). One salient observation from our studies was a detectable back-boost in pigs that were vaccinated with one antigenic phenotype and challenged with an antigenically distinct virus.…”

Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator–controlled, Randomized Superiority Trial

“…21 Possible solutions to this problem include vaccinating with strains that have drifted sufficiently from the previous vaccinating strain, and so are neutralised less effectively by circulating antibody. 22 Alternatively, in the absence of vaccine strain change, memory responses may be more effectively stimulated with adjuvants or a higher antigen dose.…”

High-resolution influenza mapping of a city reveals socioeconomic determinants of transmission within and between urban quarters

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