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

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.

[1]  E. Sanders,et al.  Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries , 2022, Frontiers in Immunology.

[2]  J. Mertsola,et al.  Pertussis toxin neutralizing antibody response after an acellular booster vaccination in Dutch and Finnish participants of different age groups , 2022, Emerging microbes & infections.

[3]  Yanping Guo,et al.  Modification of innate immune responses to Bordetella pertussis in babies from pertussis vaccinated pregnancies , 2021, EBioMedicine.

[4]  Manfred S. Green,et al.  Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women—The Role of Sex Hormones , 2021, Vaccines.

[5]  Zhiyun Chen,et al.  Determination of serum neutralizing antibodies reveals important difference in quality of antibodies against pertussis toxin in children after infection. , 2021, Vaccine.

[6]  J. van de Kassteele,et al.  Responses to an acellular pertussis booster vaccination in children, adolescents, and young and older adults: A collaborative study in Finland, the Netherlands, and the United Kingdom , 2021, EBioMedicine.

[7]  Petra E. Verburg,et al.  Safety of maternal pertussis vaccination on pregnancy and birth outcomes: A prospective cohort study. , 2020, Vaccine.

[8]  C. Locht,et al.  Quantity and quality of antibodies after acellular versus whole cell pertussis vaccines in infants born to mothers who received Tdap during pregnancy: a randomised trial. , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  P. Lambert,et al.  Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers. , 2019, Cell reports.

[10]  S. Donath,et al.  The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses , 2019, EClinicalMedicine.

[11]  C. Locht,et al.  PERISCOPE: road towards effective control of pertussis. , 2019, The Lancet. Infectious diseases.

[12]  J. van de Kassteele,et al.  Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial. , 2019, The Lancet. Infectious diseases.

[13]  G. Berbers,et al.  Antibody responses to Bordetella pertussis and other childhood vaccines in infants born to mothers who received pertussis vaccine in pregnancy – a prospective, observational cohort study from the United Kingdom , 2019, Clinical and experimental immunology.

[14]  O. Vanderkooi,et al.  A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  K. Shibayama,et al.  A high seroprevalence of antibodies to pertussis toxin among Japanese adults: Qualitative and quantitative analyses , 2017, PloS one.

[16]  P. van Damme,et al.  Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium , 2017, Virulence.

[17]  N. Hens,et al.  Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age. , 2016, Vaccine.

[18]  N. Andrews,et al.  Effectiveness of maternal pertussis vaccination in England: an observational study , 2014, The Lancet.

[19]  R. Gonen,et al.  The effect of timing of maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels - a prospective study. , 2014, Vaccine.

[20]  S. Niewiesk.  Maternal Antibodies: Clinical Significance, Mechanism of Interference with Immune Responses, and Possible Vaccination Strategies , 2014, Front. Immunol..

[21]  J. McVernon,et al.  Increased Population Prevalence of Low Pertussis Toxin Antibody Levels in Young Children Preceding a Record Pertussis Epidemic in Australia , 2012, PloS one.

[22]  C. von Hunolstein,et al.  Improved Specificity of a Multiplex Immunoassay for Quantitation of Anti-Diphtheria Toxin Antibodies with the Use of Diphtheria Toxoid , 2011, Clinical and Vaccine Immunology.

[23]  H. Hallander,et al.  Seroprevalence of pertussis antitoxin (anti-PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program , 2009, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[24]  H. Hallander,et al.  Kinetics and sensitivity of ELISA IgG pertussis antitoxin after infection and vaccination with Bordetella pertussis in young children , 2009, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[25]  G. Berbers,et al.  Development and validation of a multiplex immunoassay for the simultaneous determination of serum antibodies to Bordetella pertussis, diphtheria and tetanus. , 2008, Journal of immunological methods.

[26]  C. Siegrist.  Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants. , 2003, Vaccine.

[27]  M. Pichichero,et al.  The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids. , 1995, Pediatrics.

[28]  K. Edwards,et al.  Natural history of pertussis antibody in the infant and effect on vaccine response. , 1990, The Journal of infectious diseases.

[29]  OUP accepted manuscript , 2021, Clinical Infectious Diseases.

[30]  U. Bauer,et al.  [Centers for Disease Control and Prevention (CDC)]. , 2000, Annales de dermatologie et de venereologie.