Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa

Avnika B Amin, Marta C Nunes, Milagritos D Tapia, Shabir A Madhi, Clare L Cutland, Niteen Wairagkar, Saad B Omer, for BMGF Supported Maternal Influenza Immunization Trials Investigators Group, Avnika B Amin, Marta C Nunes, Milagritos D Tapia, Shabir A Madhi, Clare L Cutland, Niteen Wairagkar, Saad B Omer, for BMGF Supported Maternal Influenza Immunization Trials Investigators Group

Abstract

Background: A key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination.

Methods: We pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection.

Results: For all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls.

Conclusions: Our results provide robust support for further expansion of maternal influenza vaccination recommendations.

Clinical trials registration: NCT01430689 and NCT01306669.

Keywords: Immunogenicity; Influenza; Influenza vaccine; Maternal vaccination; Transplacental antibody transfer.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Timing of influenza strains used in the vaccines (Vaxigrip, Sanofi Pasteur) during each trial. The same A/H1N1 strain was used for the duration of both trials. Three different A/H3N2 strains and two different Type B strains were used.
Fig. 2
Fig. 2
Geometric mean HAI titers and factor change between measurements by vaccine group. Panels (A), (B), and (C) display the results for the A/H1N1, A/H3N2, and Type B components of the influenza vaccine, respectively. I bars indicate 95% confidence intervals. ‘Control’ indicates women who received either meningococcal vaccine or a saline injection, or their infants. ‘Vaccine’ indicates women who received trivalent inactivated influenza vaccine, or their infants. Two-sided, two-sample t-tests were used to compare the HAI titers and factor change for each component between control and IIV3 recipient groups, with a log-normal distribution specified for the titers and factor change. Abbreviations: HAI, hemagglutination-inhibition; IIV3, trivalent inactivated influenza vaccine.
Fig. 3
Fig. 3
Seroprotection, seroconversion, and transplacental antibody transfer by vaccine component. Panels (A) and (D) display the proportion of women and infants, respectively, with a seroprotective titer of at least 1:40. Panel (B) shows the proportion of women who seroconverted (at least a fourfold increase in titers) between baseline and one month post-vaccination visits. Panel (C) shows the ratio of infant:mother antibodies at birth. Two-sided exact tests were used to compare the proportion seroprotected against each vaccine component within control and vaccine recipient groups, and the proportion who seroconverted for each component between groups. Two-sided, two-sample t-tests were used to compare the transplacental transfer of hemagglutination-inhibition antibodies for each vaccine component between control and IIV3 recipient groups, with a log-normal distribution specified for transfer ratio.

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Source: PubMed

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