A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants

Abstract

Background Pertussis vaccines containing three or five pertussis antigens are recommended in pregnancy in many countries, but no studies have compared the effect on infants’ antigen-specific immunoglobulin G (IgG) concentrations. The aim of this study was to compare anti-pertussis IgG responses following primary immunization in infants of mothers vaccinated with TdaP 5 -IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP 3 -IPV in pregnancy (three pertussis antigens). Methods This multi-centre phase IV randomized clinical trial was conducted in a tertiary referral centre and primary care sites in England. Women were randomized to receive TdaP 5 -IPV ( n = 77) or TdaP 3 -IPV ( n = 77) at 28–32 gestational weeks. A non-randomized control group of 44 women who had not received a pertussis-containing vaccine in pregnancy and their 47 infants were enrolled post-partum. Results Following infant primary immunization, there was no difference in the geometric mean concentrations (GMCs) of anti-pertussis toxin, filamentous haemagglutinin or pertactin IgG between infants born to women vaccinated with TdaP 5 -IPV ( n = 67) or TdaP 3 -IPV ( n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP 5 -IPV- and TdaP 3 -IPV-vaccinated mothers compared to infants born to unvaccinated mothers ( n = 45) (geometric mean ratio 0.71 [0.56–0.90] and 0.78 [0.61–0.98], respectively); by 13 months of age, this difference was no longer observed. Conclusion Blunting of anti-pertussis toxin IgG response following primary immunization occurs in infants born to women vaccinated with TdaP 5 -IPV and TdaP 3 -IPV, with no difference between maternal vaccines. The blunting effect had resolved by 13 months of age. These results may be helpful for countries considering which pertussis-containing vaccine to recommend for use in pregnancy. Trial registration ClinicalTrials.gov , NCT02145624 , registered 23 May 2014