The Influence of Maternally Derived Antibody and Infant Age at Vaccination on Infant Vaccine Responses: An Individual Participant Meta-analysis

Voysey, Merryn; Kelly, Dominic F.; Fanshawe, Thomas R.; Sadarangani, Manish; O’Brien, Katherine L.; Perera, Rafael; Pollard, Andrew J.

doi:10.1001/jamapediatrics.2017.0638

Cited by 141Immune responses and vaccinationsImmunotherapy and Immune ResponsesBacterial Infections and Vaccines

The Influence of Maternally Derived Antibody and Infant Age at Vaccination on Infant Vaccine Responses: An Individual Participant Meta-analysis

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Voysey, Merryn, Kelly, Dominic F., Fanshawe, Thomas R., Sadarangani, Manish, O’Brien, Katherine L., Perera, Rafael, Pollard, Andrew J.·2017·JAMA Pediatrics

DOI 10.1001/jamapediatrics.2017.0638PMC PMC5710349

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Abstract

Importance: The design of infant immunization schedules requires an understanding of the factors that determine the immune response to each vaccine antigen. Data Sources: Deidentified individual participant data from GlaxoSmithKline clinical trials were obtained through Clinical Study Data Request. The data were requested on January 2, 2015, and final data were received on April 11, 2016. Study Selection: Immunogenicity trials of licensed or unlicensed vaccines administered to infants were included if antibody concentrations in infants were measured prior to the first dose of vaccine. Data Extraction and Synthesis: The database was examined; studies that appeared to have appropriate data were reviewed. Main Outcomes and Measures: Antigen-specific antibody concentration measured 1 month after priming vaccine doses, before booster vaccination, and 1 month after booster vaccine doses. Results: A total of 7630 infants from 32 studies in 17 countries were included. Mean (SD) age at baseline was 9.0 (2.3) weeks; 3906 (51.2%) were boys. Preexisting maternal antibody inhibited infant antibody responses to priming doses for 20 of 21 antigens. The largest effects were observed for inactivated polio vaccine, where 2-fold higher maternal antibody concentrations resulted in 20% to 28% lower postvaccination antibody concentration (geometric mean ratios [GMRs], type 1: 0.80; 95% CI, 0.78-0.83; type 2: 0.72; 95% CI, 0.69-0.74; type 3: 0.78; 95% CI, 0.75-0.82). For acellular pertussis antigens, 2-fold higher maternal antibody was associated with 11% lower postvaccination antibody for pertussis toxoid (GMR, 0.89; 95% CI, 0.87-0.90) and filamentous hemagglutinin (GMR, 0.89; 95% CI, 0.88-0.90) and 22% lower pertactin antibody (GMR, 0.78; 95% CI, 0.77-0.80). For tetanus and diphtheria, these estimates were 13% (GMR, 0.87; 95% CI, 0.86-0.88) and 24% (GMR, 0.76; 95% CI, 0.74-0.77), respectively. The influence of maternal antibody was still evident in reduced responses to booster doses of acellular pertussis, inactivated polio, and diphtheria vaccines at 12 to 24 months of age. Children who were older when first immunized had higher antibody responses to priming doses for 18 of 21 antigens, after adjusting for the effect of maternal antibody concentrations. The largest effect was seen for polyribosylribitol phosphate antibody, where responses were 71% higher per month (GMR, 1.71; 95% CI, 1.52-1.92). Conclusions and Relevance: Maternal antibody concentrations and infant age at first vaccination both influence infant vaccine responses. These effects are seen for almost all vaccines contained in global immunization programs and influence immune response for some vaccines even at the age of 24 months. These data highlight the potential for maternal immunization strategies to influence established infant programs.

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There is evidence that there is a physiological age-dependent increase in antibody responses in infancy.
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A guide to vaccinology: from basic principles to new developments
Pollard, A. J., & Bijker, E. M. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00479-7 · Cited by 1,593 · see citing works
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Nucleoside-modified mRNA vaccination partially overcomes maternal antibody inhibition of de novo immune responses in mice
Willis, E., Pardi, N., Parkhouse, K., Mui, B. L., Tam, Y. K., Weissman, D., & Hensley, S. E. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aav5701 · Cited by 54 · see citing works

Authors: Voysey, M., Kelly, D. F., Fanshawe, T. R., Sadarangani, M., O’Brien, K. L., Perera, R., & Pollard, A. J.
Affiliations: University of Oxford (GB)
University of British Columbia (CA)
Johns Hopkins University (US)
Corresponding author: Voysey, Merryn
ORCID: Voysey, Merryn
Kelly, Dominic F.
Fanshawe, Thomas R.
Sadarangani, Manish
O’Brien, Katherine L.
Perera, Rafael
Pollard, Andrew J.
Venue: JAMA Pediatrics
Publisher: American Medical Association (AMA)
Published: 2017-07-01
Volume: 171
Issue: 7
Pages: 637
ISSN: 1072-4710 (ISSN-L)
2168-6203
DOI: 10.1001/jamapediatrics.2017.0638
PMC: PMC5710349
OpenAlex: W2615302290
Cited by: 141
References: 44
Citations by year: 2026: 19 · 2025: 21 · 2024: 16 · 2023: 11 · 2022: 8 · 2021: 14 · 2020: 17 · 2019: 19 · 2018: 12 · 2017: 4
FWCI: 6.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Archives of Pediatrics and Adolescent Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute for Health and Care Research (DRF-2015-08-048)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords: maternal antibodies, age at vaccination, infant immunization schedule, inactivated poliovirus vaccine, acellular pertussis vaccine, tetanus toxoid, diphtheria toxoid, pertussis toxoid, filamentous hemagglutinin, pertactin, vaccine immunogenicity, antibody concentration, booster vaccination
MeSH terms: Antibodies, Bacterial, Female, Humans, Immunization Schedule, Immunization, Secondary, Infant, Male, Mothers, Vaccination

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The Influence of Maternally Derived Antibody and Infant Age at Vaccination on Infant Vaccine Responses: An Individual Participant Meta-analysis

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