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

Christine Elizabeth Jones; Anna Calvert; Joanna Southern; Mary Matheson; Nicholas Andrews; Asma Khalil; Hannah Cuthbertson; Bassam Hallis; Anna England; Paul T. Heath; Elizabeth Miller

doi:10.1186/s12916-021-02005-5

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

Christine Elizabeth Jones^*, Anna Calvert, Joanna Southern, Mary Matheson, Nicholas Andrews, Asma Khalil, Hannah Cuthbertson, Bassam Hallis, Anna England, Paul T. Heath, Elizabeth Miller

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

5 Downloads (Pure)

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 TdaP₅-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP₃-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 TdaP₅-IPV (n = 77) or TdaP₃-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 TdaP₅-IPV (n = 67) or TdaP₃-IPV (n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP₅-IPV- and TdaP₃-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 TdaP₅-IPV and TdaP₃-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

Original language	English
Article number	138
Journal	BMC Medicine
Volume	19
Issue number	1
Early online date	8 Jun 2021
DOIs	https://doi.org/10.1186/s12916-021-02005-5
Publication status	Published - Dec 2021

Bibliographical note

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.
The funder, NIHR, was not involved in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
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.

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher Copyright:© 2021, The Author(s).

Citation: Jones, C.E., Calvert, A., Southern, J. et al. 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 Med 19, 138 (2021).

DOI: https://doi.org/10.1186/s12916-021-02005-5

Keywords

Immune
Immunization
Infant
Maternal vaccination
Pregnancy
Response
Vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s12916-021-02005-5Licence: CC BY

Jones2021APhaseIVMulti-CentreRandomisedClinicalTrialBMCMedicineFinal published version, 722 KBLicence: CC BY

Cite this

Jones, C. E., Calvert, A., Southern, J., Matheson, M., Andrews, N., Khalil, A., Cuthbertson, H., Hallis, B., England, A., Heath, P. T., & Miller, E. (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]. https://doi.org/10.1186/s12916-021-02005-5

@article{c89a5b2b66334213b24360c292a469cc,

title = "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{\textquoteright} 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 TdaP5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP3-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 TdaP5-IPV (n = 77) or TdaP3-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 TdaP5-IPV (n = 67) or TdaP3-IPV (n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP5-IPV- and TdaP3-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 TdaP5-IPV and TdaP3-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",

keywords = "Immune, Immunization, Infant, Maternal vaccination, Pregnancy, Response, Vaccine",

author = "Jones, {Christine Elizabeth} and Anna Calvert and Joanna Southern and Mary Matheson and Nicholas Andrews and Asma Khalil and Hannah Cuthbertson and Bassam Hallis and Anna England and Heath, {Paul T.} and Elizabeth Miller",

note = "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. The funder, NIHR, was not involved in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. CEJ, AC, AK and PTH have conducted studies on behalf of St George{\textquoteright}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. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Publisher Copyright:{\textcopyright} 2021, The Author(s). Citation: Jones, C.E., Calvert, A., Southern, J. et al. 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 Med 19, 138 (2021). DOI: https://doi.org/10.1186/s12916-021-02005-5",

year = "2021",

month = dec,

doi = "10.1186/s12916-021-02005-5",

language = "English",

volume = "19",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central",

number = "1",

}

Jones, CE, Calvert, A, Southern, J, Matheson, M , Andrews, N, Khalil, A, Cuthbertson, H , Hallis, B , England, A, Heath, PT & Miller, E 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, vol. 19, no. 1, 138. https://doi.org/10.1186/s12916-021-02005-5

TY - JOUR

T1 - A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants

AU - Jones, Christine Elizabeth

AU - Calvert, Anna

AU - Southern, Joanna

AU - Matheson, Mary

AU - Andrews, Nicholas

AU - Khalil, Asma

AU - Cuthbertson, Hannah

AU - Hallis, Bassam

AU - England, Anna

AU - Heath, Paul T.

AU - Miller, Elizabeth

N1 - 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. The funder, NIHR, was not involved in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. 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. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Publisher Copyright:© 2021, The Author(s). Citation: Jones, C.E., Calvert, A., Southern, J. et al. 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 Med 19, 138 (2021). DOI: https://doi.org/10.1186/s12916-021-02005-5

PY - 2021/12

Y1 - 2021/12

N2 - 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 TdaP5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP3-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 TdaP5-IPV (n = 77) or TdaP3-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 TdaP5-IPV (n = 67) or TdaP3-IPV (n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP5-IPV- and TdaP3-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 TdaP5-IPV and TdaP3-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

AB - 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 TdaP5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP3-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 TdaP5-IPV (n = 77) or TdaP3-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 TdaP5-IPV (n = 67) or TdaP3-IPV (n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP5-IPV- and TdaP3-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 TdaP5-IPV and TdaP3-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

KW - Immune

KW - Immunization

KW - Infant

KW - Maternal vaccination

KW - Pregnancy

KW - Response

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=85107568907&partnerID=8YFLogxK

U2 - 10.1186/s12916-021-02005-5

DO - 10.1186/s12916-021-02005-5

M3 - Article

C2 - 34098951

AN - SCOPUS:85107568907

VL - 19

JO - BMC Medicine

JF - BMC Medicine

SN - 1741-7015

IS - 1

M1 - 138

ER -

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

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this