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An updated influenza A(H3N2) vaccine generates limited antibody responses to previously encountered antigens in children.

ABSTRACT: BACKGROUND:Influenza vaccination may provide a "back-boost" to antibodies against previously encountered strains. If the back-boost effect is common, this could allow more aggressive vaccine updates, as emerging variants would be expected to both elicit de-novo responses and boost pre-existing responses against recently circulating strains. Here we used the emergence of an antigenically novel A(H3N2) strain to determine whether an antigenically updated vaccine boosted antibodies against historical strains. METHODS:We performed hemagglutination-inhibition (HI) assays on pre- and post-vaccination sera from 124 children 5-17?years old who received 2015-2016 inactivated influenza vaccine, containing an antigenically updated A(H3N2) strain. We evaluated the mean fold increase in HI titer against both the 2015-2016 vaccine strain and representative strains from two prior antigenic clusters. Factors associated with post-vaccination titers against historical strains were evaluated using linear regression, adjusting for baseline titer. RESULTS:Geometric mean titers against each antigen examined increased significantly after vaccination (P?

SUBMITTER: Florek NW

PROVIDER: S-EPMC5773382 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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An updated influenza A(H3N2) vaccine generates limited antibody responses to previously encountered antigens in children.

Florek Kelsey R KR Campos Luiza M LM Braun Katarina M KM McLean Huong Q HQ King Jennifer P JP Flannery Brendan B Belongia Edward A EA Friedrich Thomas C TC

Vaccine 20171215 5

<h4>Background</h4>Influenza vaccination may provide a "back-boost" to antibodies against previously encountered strains. If the back-boost effect is common, this could allow more aggressive vaccine updates, as emerging variants would be expected to both elicit de-novo responses and boost pre-existing responses against recently circulating strains. Here we used the emergence of an antigenically novel A(H3N2) strain to determine whether an antigenically updated vaccine boosted antibodies against ...[more]

PMID: 29249543

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Project description:Older adults experience declining influenza vaccine-induced immunity and are at higher risk of influenza and its complications. For this reason, high dose (e.g., Fluzone) and adjuvanted (e.g., Fluad) vaccines are preferentially recommended for people age 65 years and older. However, T cell transcriptional activity shaping the humoral immune responses to Fluzone and Fluad vaccines in older adults is still poorly understood. We designed a study of 234 older adults (≥65 years old) who were randomly allocated to receive Fluzone or Fluad vaccine and provided blood samples at baseline and at Day 28 after immunization. We measured the humoral immune responses (hemagglutination inhibition/HAI antibody titer) to influenza A/H3N2 and performed mRNA-Seq transcriptional profiling in purified CD4+ T cells, in order to identify T cell signatures that might explain differences in humoral immune response by vaccine type. Given the large differences in formulation (higher antigen dose vs adjuvant), our hypothesis was that each vaccine elicited a distinct transcriptomic response after vaccination. Thus, the main focus of our study was to identify the differential gene expression influencing the antibody titer in the two vaccine groups. Our analyses identified three differentially expressed, functionally linked genes/proteins in CD4+ T cells: the calcium/calmodulin dependent serine/threonine kinase IV (CaMKIV); its regulator the TMEM38B/transmembrane protein 38B, involved in maintenance of intracellular Ca2+ release; and the transcriptional coactivator CBP/CREB binding protein, as regulators of transcriptional activity/function in CD4+ T cells that impact differences in immune response by vaccine type. Significantly enriched T cell-specific pathways/biological processes were also identified that point to the importance of genes/proteins involved in Th1/Th2 cell differentiation, IL-17 signaling, calcium signaling, Notch signaling, MAPK signaling, and regulation of TRP cation Ca2+ channels in humoral immunity after influenza vaccination. In summary, we identified the genes/proteins and pathways essential for cell activation and function in CD4+ T cells that are associated with differences in influenza vaccine-induced humoral immunity by vaccine type. These findings provide an additional mechanistic perspective for achieving protective immunity in older adults.

Project description:Human influenza A viruses are rapidly evolving pathogens that cause substantial morbidity and mortality in seasonal epidemics around the globe. To ensure continued protection, the strains used for the production of the seasonal influenza vaccine have to be regularly updated, which involves data collection and analysis by numerous experts worldwide. Computer-guided analysis is becoming increasingly important in this problem due to the vast amounts of generated data. We here describe a computational method for selecting a suitable strain for production of the human influenza A virus vaccine. It interprets available antigenic and genomic sequence data based on measures of antigenic novelty and rate of propagation of the viral strains throughout the population. For viral isolates sampled between 2002 and 2007, we used this method to predict the antigenic evolution of the H3N2 viruses in retrospective testing scenarios. When seasons were scored as true or false predictions, our method returned six true positives, three false negatives, eight true negatives, and one false positive, or 78% accuracy overall. In comparison to the recommendations by the WHO, we identified the correct antigenic variant once at the same time and twice one season ahead. Even though it cannot be ruled out that practical reasons such as lack of a sufficiently well-growing candidate strain may in some cases have prevented recommendation of the best-matching strain by the WHO, our computational decision procedure allows quantitative interpretation of the growing amounts of data and may help to match the vaccine better to predominating strains in seasonal influenza epidemics. Importance: Human influenza A viruses continuously change antigenically to circumvent the immune protection evoked by vaccination or previously circulating viral strains. To maintain vaccine protection and thereby reduce the mortality and morbidity caused by infections, regular updates of the vaccine strains are required. We have developed a data-driven framework for vaccine strain prediction which facilitates the computational analysis of genetic and antigenic data and does not rely on explicit evolutionary models. Our computational decision procedure generated good matches of the vaccine strain to the circulating predominant strain for most seasons and could be used to support the expert-guided prediction made by the WHO; it thus may allow an increase in vaccine efficacy.

Dataset Information

An updated influenza A(H3N2) vaccine generates limited antibody responses to previously encountered antigens in children.

Publications

An updated influenza A(H3N2) vaccine generates limited antibody responses to previously encountered antigens in children.

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