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High-dose influenza vaccine favors acute plasmablast responses rather than long-term cellular responses.

ABSTRACT: High-dose (HD) influenza vaccine shows improved relative efficacy against influenza disease compared to standard-dose (SD) vaccine in individuals ?65years. This has been partially credited to superior serological responses, but a comprehensive understanding of cell-mediated immunity (CMI) of HD vaccine remains lacking. In the current study, a total of 105 participants were randomly administered HD or SD vaccine and were evaluated for serological responses. Subsets of the group (n=12-26 per group) were evaluated for B and T cell responses at days 0, 7, 14 and 28 post-vaccination by flow cytometry or ELISPOT assay. HD vaccine elicited significantly higher hemagglutination inhibition (HI) titers than SD vaccine at d28, but comparable titers at d365 post-vaccination. HD vaccine also elicited higher vaccine-specific plasmablast responses at d7 post-vaccination than SD vaccine. However, long-lived memory B cell induction, cytokine-secreting T cell responses and persistence of serological memory were comparable regardless of vaccine dose. More strategies other than increased Ag amount may be needed to improve CMI in older adults.ClinicalTrials.gov NCT 01189123.

SUBMITTER: Kim JH

PROVIDER: S-EPMC4996724 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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High-dose influenza vaccine favors acute plasmablast responses rather than long-term cellular responses.

Kim Jin Hyang JH Talbot H Keipp HK Mishina Margarita M Zhu Yuwei Y Chen Jufu J Cao Weiping W Reber Adrian J AJ Griffin Marie R MR Shay David K DK Spencer Sarah M SM Sambhara Suryaprakash S

Vaccine 20160726 38

<h4>Unlabelled</h4>High-dose (HD) influenza vaccine shows improved relative efficacy against influenza disease compared to standard-dose (SD) vaccine in individuals ⩾65years. This has been partially credited to superior serological responses, but a comprehensive understanding of cell-mediated immunity (CMI) of HD vaccine remains lacking. In the current study, a total of 105 participants were randomly administered HD or SD vaccine and were evaluated for serological responses. Subsets of the group ...[more]

PMID: 27473306

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Project description:The normal response to influenza A infection is to remain asymptomatic; indeed, a study of volunteers who tested positive for antibodies against 2009 H1N1 revealed that a majority did not experience symptoms. However, studies of influenza pandemics since the 20th century, and to a lesser degree seasonal flu, suggest that pregnancy increases influenza-associated morbidity and mortality. The confounding effect of pregnancy has been well established to adversely alter the clinical course of influenza, with short term complications to mother and baby apparent, and long-term consequences to the fetus hypothesized. However, how the condition of pregnancy impacts long-term maternal anti-influenza immunity remains contentious; while vaccination studies suggest humoral responses sufficient for protection, published research on adaptive immune responses against influenza formed during pregnancy is limited. This study expands upon published work from our lab and others by comprehensively examining compartmental and systemic changes following pandemic A/California/07/2009 influenza infection. Previously, we linked seasonal influenza infection to clinical observations of adverse outcomes in pregnancy, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we observe that the results of a lower infectious dose of pandemic influenza are similar to that of seasonal influenza. Importantly, we expand upon work which suggests infection during pregnancy may also affect humoral immunity. Our observations of reduced early antibody hemagglutinin inhibition and virus neutralization which resolved within 8 weeks of delivery demonstrate that influenza infection impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This hypothesis is further supported by plasmablast transcriptional data, which demonstrates downregulated B cell metabolism and post-translational modification systems only among pregnant animals. These findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during influenza infection, and propose resolving humoral deficiencies following influenza infection confounded by pregnancy. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.

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High-dose influenza vaccine favors acute plasmablast responses rather than long-term cellular responses.

Publications

High-dose influenza vaccine favors acute plasmablast responses rather than long-term cellular responses.

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