Abstract

ObjectivesInfluenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women.Study DesignImmune responses were measured in healthy pregnant R620W carrier (n = 17) and non-carrier (n = 33) women receiving the 2013 quadrivalent inactivated influenza vaccine (Fluzone). Hemagglutination inhibition assays were performed to quantify neutralizing antibodies; functional influenza-reactive CD4 T cells were quantified by flow cytometry, and influenza-specific CD8 T cells were enumerated with MHC Class I tetramers. Antibody seroconversion data were evaluated by Chi-square analysis, and the Mann-Whitney or Wilcoxon signed-rank tests were applied to T cell response data.ResultsPTPN22 R620W carrier (n = 17) and non-carrier (n = 33) groups did not differ in age, parity, BMI, gestational age at time of vaccine, or history of prior influenza vaccination. After Fluzone exposure, 51.5% of non-carriers met criteria for antibody seroconversion to H1N1 influenza, compared with 23.5% of R620W carriers (p = 0.06). Influenza-reactive CD4 T cells showed modest increase at days 9–15 after vaccination in both R620W carriers and non-carriers (p = 0.02 and p = 0.04, respectively). However, there was no difference in overall response between the two groups (p = 0.6). The vaccine did not result in significant induction of influenza-specific CD8 T cells in either group.ConclusionsThere was no significant difference among healthy pregnant R620W carriers and non-carriers in H1N1 antibody seroconversion rates after influenza vaccination. Studies of larger cohorts will be needed to define the effect of PTPN22 risk allele carriage on antibody and T cell responses to influenza vaccination during pregnancy.

Highlights

  • Pregnancy is a well-recognized risk factor for heightened susceptibility to, and increased severity of, respiratory and other infections

  • Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) R620W carrier (n = 17) and non-carrier (n = 33) groups did not differ in age, parity, BMI, gestational age at time of vaccine, or history of prior influenza vaccination

  • There was no significant difference among healthy pregnant R620W carriers and non-carriers in H1N1 antibody seroconversion rates after influenza vaccination

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Summary

Introduction

Pregnancy is a well-recognized risk factor for heightened susceptibility to, and increased severity of, respiratory and other infections. Hormonal and immunologic variations in pregnancy likely play a crucial role in both infectious disease susceptibility and severity [2]. In pregnant women, seasonal influenza infection remains a significant cause of respiratory morbidity and mortality in the United States [3]. Given the tremendous disease burden reflected in pregnant populations, and observations that influenza vaccination during pregnancy can reduce the risk of influenza infection by 50% [8], both the CDC and the American College of Obstetricians and Gynecologists recommend annual inactivated influenza vaccination for all pregnant women [9,10], typically as soon as possible in pregnancy

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