Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine

Abstract

Background: Inactivated influenza vaccine (IIV) is recommended during pregnancy to prevent influenza infection and its complications in pregnant women and their infants. However, the extent to which pregnancy modifies the antibody response to vaccination remains unclear, and prior studies have focused primarily on hemagglutinin inhibition (HI) titers. A more comprehensive understanding of how pregnancy modifies the humoral immune response to influenza vaccination will aid in maximizing vaccine efficacy.

Methods: Healthy pregnant women and control women were studied prior to, 7 days after, and 28 days after vaccination with IIV. HI titers, microneutralization (MN) titers, and the frequency of circulating plasmablasts were evaluated in pregnant versus control women.

Results: Pregnant women and control women mount similarly robust serologic immune responses to IIV, with no significant differences for any influenza strain in postvaccination geometric mean HI or MN titers. HI and MN titers correlate, though MN titers demonstrate more robust changes pre- versus postvaccination. The induction of circulating plasmablasts is increased in pregnant women versus controls (median fold-change 2.60 vs 1.49 [interquartile range, 0.94-7.53 vs 0.63-2.67]; P = .03).

Conclusions: Pregnant women do not have impaired humoral immune responses to IIV and may have increased circulating plasmablast production compared to control women.

Keywords: hemagglutinin inhibition; influenza; plasmablast; pregnancy; vaccination; viral neutralization.

Figure 1.

HI titers to A/H1N1/California/2009 (pH1N1) (A), A/H3N2/Victoria/2011 (B), and B/Wisconsin/2010 (C) before (Day 0) and after (Day 28) IIV administration in pregnant and control women. Titers are the reciprocal of the highest serum dilution capable of preventing hemagglutination of red blood cells. Lines connect data points from individuals. Data points represent average of technical replicates. Abbreviations: HI, hemagglutination inhibition; IIV, inactivated influenza vaccine.

Figure 2.

MN titers to A/H1N1/California/2009 (pH1N1) (A), A/H3N2/Victoria/2011 (B), and B/Wisconsin/2010 (C) before (Day 0) and after (Day 28) IIV administration in pregnant and control women. Titers are the reciprocal of the highest serum dilution factor with less than 50% infection, normalized to positive controls. Lines connect data points from individuals. Data points represent average of technical replicates. Abbreviations: IIV, inactivated influenza vaccine; MN, microneutralization.

Figure 3.

Total serum IgG concentrations in pregnant and control women, before and after IIV. Pre- and postvaccination levels were compared using a Mann–Whitney U test. Error bars represent geometric mean with 95% confidence intervals. Abbreviations: IgG, immunoglobin G; IIV, inactivated influenza vaccine.

Figure 4.

B-cell frequencies as a percentage of live PBMCs in control (circles) and pregnant (triangles) women prevaccination, 7 days postvaccination, 28 days postvaccination, and 6 weeks postpartum in the pregnant group. Abbreviations: PBMCs, peripheral blood mononuclear cells; PP, postpartum.

Figure 5.

Plasmablast frequencies in pregnant women and controls. A, Plasmablast frequencies prevaccination and 7 days postvaccination in control (circles) and pregnant (triangles) were compared longitudinally using a Wilcoxon rank-sum test. B, Plasmablast frequencies at 7 days postvaccination and fold-changes (day 7 postvaccination/prevaccination) were compared by Mann–Whitney U test in control and pregnant women. All error bars indicate the median and interquartile range. Abbreviations: C, control; P, pregnant.