A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants
A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants
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
Immune, Immunization, Infant, Maternal vaccination, Pregnancy, Response, Vaccine
Jones, Christine E
48229079-8b58-4dcb-8374-d9481fe7b426
Calvert, Anna
03bc971b-ed4f-4c6c-bcb5-29943bff1661
Southern, Jo
caf11713-98a0-49c6-a403-b297319aeae3
Matheson, Mary
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Andrews, Nick
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Khalil, Asma
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Cuthbertson, Hannah
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Hallis, Bassam
f6388da1-bf85-457f-b30a-c0849034024c
England, Anna
d843e84f-0d7a-4e4b-901c-e93ee549c865
Heath, Paul T.
fce44186-c98d-4bdf-8d60-d0f89fff2ce9
Miller, Elizabeth
180cf79e-2de5-4cc4-bba4-c1610d5b5036
December 2021
Jones, Christine E
48229079-8b58-4dcb-8374-d9481fe7b426
Calvert, Anna
03bc971b-ed4f-4c6c-bcb5-29943bff1661
Southern, Jo
caf11713-98a0-49c6-a403-b297319aeae3
Matheson, Mary
b0fa9c00-9320-49ef-827f-2aca908f206e
Andrews, Nick
1759d81f-6024-4945-97a9-88535e02edeb
Khalil, Asma
93c83da8-a44d-4294-b4c2-be2e6bed0731
Cuthbertson, Hannah
a2ed2e68-bad2-4215-8170-7347ccaa08eb
Hallis, Bassam
f6388da1-bf85-457f-b30a-c0849034024c
England, Anna
d843e84f-0d7a-4e4b-901c-e93ee549c865
Heath, Paul T.
fce44186-c98d-4bdf-8d60-d0f89fff2ce9
Miller, Elizabeth
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Jones, Christine E, Calvert, Anna, Southern, Jo, Matheson, Mary, Andrews, Nick, Khalil, Asma, Cuthbertson, Hannah, Hallis, Bassam, England, Anna, Heath, Paul T. and Miller, Elizabeth
(2021)
A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants.
BMC Medicine, 19 (1), [138].
(doi:10.1186/s12916-021-02005-5).
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
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iMAP2 BMC Medicine 20210510 Revisions
- Accepted Manuscript
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Figure 1_iMAP2 BMC revised
- Accepted Manuscript
More information
Accepted/In Press date: 11 May 2021
e-pub ahead of print date: 8 June 2021
Published date: December 2021
Additional Information:
Funding Information:
CEJ, AC, AK and PTH have conducted studies on behalf of St George’s, University of London and the University of Southampton and University Hospital Southampton NHS Foundation Trust (CEJ) funded by vaccine manufacturers, including Novavax and GlaxoSmithKline within the last 3 years, but receive no personal funding from these sources.
Funding Information:
This study is independent research funded by the National Institute for Health Research (NIHR) Policy Research Programme (Vaccine Evaluation Consortium Phase II, 039/0031—grant holder EM). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
Funding Information:
We thank the mothers and infants who took part in this study; the Vaccine Research Nurses in Hertfordshire and Gloucestershire for their assistance in the recruitment and follow-up of the study participants and data management; the Cord Blood team at St George?s University Hospitals NHS Foundation Trust for the support in obtaining cord blood samples from participants; the scientists at Public Health England, Porton, for testing the samples; Pauline Waight for her help with data management; Dr Shamez Ladhani and Dr Gayatri Amirthalingam for helpful discussions on the study design; and the clerical staff in the Immunization and Countermeasures Division for the study administration and data entry.
Publisher Copyright:
© 2021, The Author(s).
Keywords:
Immune, Immunization, Infant, Maternal vaccination, Pregnancy, Response, Vaccine
Identifiers
Local EPrints ID: 449204
URI: http://eprints.soton.ac.uk/id/eprint/449204
ISSN: 1741-7015
PURE UUID: 2fca9735-d223-4e0e-9470-f8741474f626
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Date deposited: 19 May 2021 18:18
Last modified: 06 Jun 2024 04:06
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Contributors
Author:
Anna Calvert
Author:
Jo Southern
Author:
Mary Matheson
Author:
Nick Andrews
Author:
Asma Khalil
Author:
Hannah Cuthbertson
Author:
Bassam Hallis
Author:
Anna England
Author:
Paul T. Heath
Author:
Elizabeth Miller
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