Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial

Federico Martinón-Torres; Scott A. Halperin; Terry Nolan; Bruce Tapiéro; Kirsten P. Perrett; Ignacio Salamanca de la Cueva; José García-Sicilia; Zbynek Stranak; Otto G. Vanderkooi; Pavel Kosina; Sarka Rumlarova; Miia Virta; Jose M.Merino Arribas; Mariano Miranda-Valdivieso; Begoña Arias Novas; Jan Bozensky; María José Cilleruelo Ortega; Jose Tomas Ramos Amador; Manuel Baca; Esperanza Escribano Palomino; Gian Vincenzo Zuccotti; Jan Janota; Paola Giovanna Marchisio; Lusine Kostanyan; Nadia Meyer; Maria Angeles Ceregido; Brigitte Cheuvart; Sherine O. Kuriyakose; Narcisa Mesaros

doi:10.1016/j.vaccine.2021.02.001

Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial

Federico Martinón-Torres
, Scott A. Halperin
, Terry Nolan
, Bruce Tapiéro
, Kirsten P. Perrett
, Ignacio Salamanca de la Cueva
, José García-Sicilia
, Zbynek Stranak
, Otto G. Vanderkooi
, Pavel Kosina
, Sarka Rumlarova
, Miia Virta
, Jose M.Merino Arribas
, Mariano Miranda-Valdivieso
, Begoña Arias Novas
, Jan Bozensky
, María José Cilleruelo Ortega
, Jose Tomas Ramos Amador
, Manuel Baca
, Esperanza Escribano Palomino

Gian Vincenzo Zuccotti, Jan Janota, Paola Giovanna Marchisio, Lusine Kostanyan, Nadia Meyer^*, Maria Angeles Ceregido, Brigitte Cheuvart, Sherine O. Kuriyakose, Narcisa Mesaros

^*Corresponding author for this work

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

11 Citations (Scopus)

32 Downloads (Pure)

Abstract

Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 27^0/7–36^6/7 weeks’ gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929.

Original language	English
Pages (from-to)	1598-1608
Number of pages	11
Journal	Vaccine
Volume	39
Issue number	11
DOIs	https://doi.org/10.1016/j.vaccine.2021.02.001
Publication status	Published - 12 Mar 2021
Publication type	A1 Journal article-refereed

Funding

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BAN reports grants from the GSK group of companies (GSK) and support from other vaccine manufacturers. BC, MAC, NMes, NMey and SOK are employees of GSK, and BC, MAC and NMes own GSK restricted shares. FMT, JGS, SAH, TN and KPP’s institutions received grants from GSK during the conduct of the study. FMT’s institution received financial and non-financial support from Ablynx, Astra Zeneca, GSK, Jansen, MedImmune, MSD, Novavax, Pfizer, Regeneron, Roche, Sanofi Pasteur and Seqirus outside the submitted work. SAH received honoraria for participation in ad-hoc advisory committees for GSK and Sanofi Pasteur. TN received personal fees from GSK for serving as chair of advisory committees outside the submitted work. BT’s institution received grants from GSK during the conduct of the study; research grants for clinical trials were also given to his institution by Pfizer, MSD and Sanofi Pasteur. KPP received a fellowship from National Health and Medical Research Council for conducting the present work, and her institution received financial support from DBV Technologies, Medlmmune, Novavax and Pfizer for conducting trials outside the submitted work. ISC has received grants and/or honoraria as a consultant/advisor or to attend conferences and practical courses from GSK, Sanofi Pasteur, MSD and Pfizer outside the submitted work. JMMA reports receiving fees and non-financial support from GSK, as well as fees from Pfizer and MSD outside the submitted work. LK is working as consultant for GSK. MB, JB, MJCO, EEP, JJ, MMV, PK, PGM, JTRA, SR, ZS, MV, OGV and GVZ declare no conflicts of interest.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Blunting
Booster
Maternal immunization
Pertussis
Tdap vaccine
Toddlers

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

Access to Document

10.1016/j.vaccine.2021.02.001Licence: CC BY

1-s2.0-S0264410X21001304-mainFinal published version, 735 KBLicence: CC BY

http://urn.fi/URN:NBN:fi:tuni-202105044399Licence: CC BY

Cite this

Martinón-Torres, F., Halperin, S. A., Nolan, T., Tapiéro, B., Perrett, K. P., de la Cueva, I. S., García-Sicilia, J., Stranak, Z., Vanderkooi, O. G., Kosina, P., Rumlarova, S., Virta, M., Arribas, J. M. M., Miranda-Valdivieso, M., Novas, B. A., Bozensky, J., Ortega, M. J. C., Amador, J. T. R., Baca, M., ... Mesaros, N. (2021). Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial. Vaccine, 39(11), 1598-1608. https://doi.org/10.1016/j.vaccine.2021.02.001

@article{591e5b66957b4ce2b1edd82074a65ac4,

title = "Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial",

abstract = "Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks{\textquoteright} gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1\% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2\% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929.",

keywords = "Blunting, Booster, Maternal immunization, Pertussis, Tdap vaccine, Toddlers",

author = "Federico Martin{\'o}n-Torres and Halperin, \{Scott A.\} and Terry Nolan and Bruce Tapi{\'e}ro and Perrett, \{Kirsten P.\} and \{de la Cueva\}, \{Ignacio Salamanca\} and Jos{\'e} Garc{\'i}a-Sicilia and Zbynek Stranak and Vanderkooi, \{Otto G.\} and Pavel Kosina and Sarka Rumlarova and Miia Virta and Arribas, \{Jose M.Merino\} and Mariano Miranda-Valdivieso and Novas, \{Bego{\~n}a Arias\} and Jan Bozensky and Ortega, \{Mar{\'i}a Jos{\'e} Cilleruelo\} and Amador, \{Jose Tomas Ramos\} and Manuel Baca and Palomino, \{Esperanza Escribano\} and Zuccotti, \{Gian Vincenzo\} and Jan Janota and Marchisio, \{Paola Giovanna\} and Lusine Kostanyan and Nadia Meyer and Ceregido, \{Maria Angeles\} and Brigitte Cheuvart and Kuriyakose, \{Sherine O.\} and Narcisa Mesaros",

note = "Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BAN reports grants from the GSK group of companies (GSK) and support from other vaccine manufacturers. BC, MAC, NMes, NMey and SOK are employees of GSK, and BC, MAC and NMes own GSK restricted shares. FMT, JGS, SAH, TN and KPP{\textquoteright}s institutions received grants from GSK during the conduct of the study. FMT{\textquoteright}s institution received financial and non-financial support from Ablynx, Astra Zeneca, GSK, Jansen, MedImmune, MSD, Novavax, Pfizer, Regeneron, Roche, Sanofi Pasteur and Seqirus outside the submitted work. SAH received honoraria for participation in ad-hoc advisory committees for GSK and Sanofi Pasteur. TN received personal fees from GSK for serving as chair of advisory committees outside the submitted work. BT{\textquoteright}s institution received grants from GSK during the conduct of the study; research grants for clinical trials were also given to his institution by Pfizer, MSD and Sanofi Pasteur. KPP received a fellowship from National Health and Medical Research Council for conducting the present work, and her institution received financial support from DBV Technologies, Medlmmune, Novavax and Pfizer for conducting trials outside the submitted work. ISC has received grants and/or honoraria as a consultant/advisor or to attend conferences and practical courses from GSK, Sanofi Pasteur, MSD and Pfizer outside the submitted work. JMMA reports receiving fees and non-financial support from GSK, as well as fees from Pfizer and MSD outside the submitted work. LK is working as consultant for GSK. MB, JB, MJCO, EEP, JJ, MMV, PK, PGM, JTRA, SR, ZS, MV, OGV and GVZ declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 GlaxoSmithKline Biologicals SA",

year = "2021",

month = mar,

day = "12",

doi = "10.1016/j.vaccine.2021.02.001",

language = "English",

volume = "39",

pages = "1598--1608",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

number = "11",

}

Martinón-Torres, F, Halperin, SA, Nolan, T, Tapiéro, B, Perrett, KP, de la Cueva, IS, García-Sicilia, J, Stranak, Z, Vanderkooi, OG, Kosina, P, Rumlarova, S, Virta, M, Arribas, JMM, Miranda-Valdivieso, M, Novas, BA, Bozensky, J, Ortega, MJC, Amador, JTR, Baca, M, Palomino, EE, Zuccotti, GV, Janota, J, Marchisio, PG, Kostanyan, L, Meyer, N, Ceregido, MA, Cheuvart, B, Kuriyakose, SO & Mesaros, N 2021, 'Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial', Vaccine, vol. 39, no. 11, pp. 1598-1608. https://doi.org/10.1016/j.vaccine.2021.02.001

TY - JOUR

T1 - Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers

T2 - Follow-up of a randomized trial

AU - Martinón-Torres, Federico

AU - Halperin, Scott A.

AU - Nolan, Terry

AU - Tapiéro, Bruce

AU - Perrett, Kirsten P.

AU - de la Cueva, Ignacio Salamanca

AU - García-Sicilia, José

AU - Stranak, Zbynek

AU - Vanderkooi, Otto G.

AU - Kosina, Pavel

AU - Rumlarova, Sarka

AU - Virta, Miia

AU - Arribas, Jose M.Merino

AU - Miranda-Valdivieso, Mariano

AU - Novas, Begoña Arias

AU - Bozensky, Jan

AU - Ortega, María José Cilleruelo

AU - Amador, Jose Tomas Ramos

AU - Baca, Manuel

AU - Palomino, Esperanza Escribano

AU - Zuccotti, Gian Vincenzo

AU - Janota, Jan

AU - Marchisio, Paola Giovanna

AU - Kostanyan, Lusine

AU - Meyer, Nadia

AU - Ceregido, Maria Angeles

AU - Cheuvart, Brigitte

AU - Kuriyakose, Sherine O.

AU - Mesaros, Narcisa

N1 - Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BAN reports grants from the GSK group of companies (GSK) and support from other vaccine manufacturers. BC, MAC, NMes, NMey and SOK are employees of GSK, and BC, MAC and NMes own GSK restricted shares. FMT, JGS, SAH, TN and KPP’s institutions received grants from GSK during the conduct of the study. FMT’s institution received financial and non-financial support from Ablynx, Astra Zeneca, GSK, Jansen, MedImmune, MSD, Novavax, Pfizer, Regeneron, Roche, Sanofi Pasteur and Seqirus outside the submitted work. SAH received honoraria for participation in ad-hoc advisory committees for GSK and Sanofi Pasteur. TN received personal fees from GSK for serving as chair of advisory committees outside the submitted work. BT’s institution received grants from GSK during the conduct of the study; research grants for clinical trials were also given to his institution by Pfizer, MSD and Sanofi Pasteur. KPP received a fellowship from National Health and Medical Research Council for conducting the present work, and her institution received financial support from DBV Technologies, Medlmmune, Novavax and Pfizer for conducting trials outside the submitted work. ISC has received grants and/or honoraria as a consultant/advisor or to attend conferences and practical courses from GSK, Sanofi Pasteur, MSD and Pfizer outside the submitted work. JMMA reports receiving fees and non-financial support from GSK, as well as fees from Pfizer and MSD outside the submitted work. LK is working as consultant for GSK. MB, JB, MJCO, EEP, JJ, MMV, PK, PGM, JTRA, SR, ZS, MV, OGV and GVZ declare no conflicts of interest. Publisher Copyright: © 2021 GlaxoSmithKline Biologicals SA

PY - 2021/3/12

Y1 - 2021/3/12

N2 - Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks’ gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929.

AB - Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks’ gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929.

KW - Blunting

KW - Booster

KW - Maternal immunization

KW - Pertussis

KW - Tdap vaccine

KW - Toddlers

U2 - 10.1016/j.vaccine.2021.02.001

DO - 10.1016/j.vaccine.2021.02.001

M3 - Article

C2 - 33612341

AN - SCOPUS:85101155159

SN - 0264-410X

VL - 39

SP - 1598

EP - 1608

JO - Vaccine

JF - Vaccine

IS - 11

ER -

Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial

Abstract

Funding

UN SDGs

Keywords

Publication forum classification

ASJC Scopus subject areas

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Cite this