Effect of immunization during pregnancy and pre-existing immunity on diphtheria-tetanus-acellular pertussis vaccine responses in infants

Emerg Microbes Infect. 2023 Dec;12(1):2204146. doi: 10.1080/22221751.2023.2204146.

Abstract

Immunization during pregnancy (IP) against pertussis is recommended in many countries to protect infants. Although maternal antibodies can influence the infants' antibody responses to primary vaccinations, their effect on the development of functional antibodies and B cells remain poorly studied. We investigated the maternal immune response to IP and the effect of IP and pre-existing antibodies on infants' primary vaccine responses in an open-label, non-randomized trial. Forty-seven mothers received tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy, and 22 mothers were included as controls. Sixty-nine infants received primary doses of DTaP at three and five months of age. Geometric mean concentrations of antibodies to pertussis toxin, filamentous haemagglutinin, pertactin, diphtheria, and tetanus toxins, pertussis toxin neutralizing antibodies (PTNAs), and plasma and memory B-cell frequencies were studied at delivery, and at three, five and six months. Levels of antibodies, PTNAs, and frequencies of memory B-cells were significantly increased at delivery and up to six months after in mothers with IP compared to those without IP (all p < 0.05, except for PT-specific memory B-cells). In vaccinated pregnant women, high pre-existing antibody levels were positively correlated with higher antibody responses after IP. IP blunted the infants' antibody and plasma B-cell responses to all vaccine antigens, except for tetanus toxin. This blunting effect was the strongest in infants with high concentrations of maternal antibodies. In conclusion, IP resulted in significantly higher concentrations of antibodies in infants up to three months of age (all p < 0.05); but was associated with blunting of various infants' vaccine responses.

Keywords: Immunization in pregnancy; antibodies; infants; memory B cells; pertussis; pertussis toxin neutralization; primary vaccination.

MeSH terms

  • Antibodies, Bacterial
  • Diphtheria*
  • Diphtheria-Tetanus-acellular Pertussis Vaccines*
  • Female
  • Humans
  • Immunization
  • Infant
  • Pertussis Toxin
  • Pregnancy
  • Vaccination / methods
  • Whooping Cough* / prevention & control

Substances

  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Pertussis Toxin
  • Antibodies, Bacterial

Grants and funding

This work was supported by the PERISCOPE (pertussis correlates of protection Europe) project. The PERISCOPE project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 115910. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme; the European Federation of Pharmaceutical Industries and Associations; and Bill & Melinda Gates Foundation. The supporters of this study did not have any role in the data collection, analysis, interpretation of the data, nor in the writing of the report; IMI2 Periscope.