BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.

Alberta Children's Hospital University of Calgary Alberta Calgary Canada

CHU Sainte Justine Université de Montréal Montréal Canada

Dalhousie University Canadian Center for Vaccinology Halifax Canada

GSK Bangalore India

GSK Wavre Belgium

Hospital Clínico San Carlos Madrid Spain

Hospital HM Puerta del Sur Móstoles Spain

Hospital La Paz Madrid Spain

Hospital Monteprincipe Boadilla del Monte Spain

Hospital Quirónsalud Málaga Málaga Spain

Hospital Universitario Puerta de Hierro Majadahonda Spain

Institute for the Care of Mother and Child Prague Czech Republic

Instituto Sevillano de la Mujer Instituto Hispalense de Pediatría Seville Spain

Modis C O GSK Wavre Belgium

Murdoch Children's Research Institute and Melbourne School of Population and Global Health University of Melbourne Melbourne Australia

Nuevo Hospital Universitario de Burgos Burgos Spain

Ospedale dei Bambini Vittore Buzzi and University of Milan Milan Italy

Ospedale Ostetrico Ginecologico Sant'Anna Turin Italy and Department of Maternal Infant Pediatric Health Degli Infermi Hospital Biella Italy

Tampere Vaccine Research Center Tampere University Tampere Finland

Translational Pediatrics and Infectious Diseases Pediatrics Department Hospital Clínico Universitario de Santiago de Compostela and Genetics Vaccines and Pediatrics Research Group University of Santiago de Compostela Instituto de Investigación Sanitaria de Santiago de Compostela Santiago de Compostela Spain

Universidad Francisco de Vitoria Madrid Spain

Università degli Studi di Milano Milan Italy

University Hospital Hradec Kralove Czech Republic

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$a Perrett, Kirsten P $u Murdoch Children's Research Institute and Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. Electronic address: kirsten.perrett@rch.org.au

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$a Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial / $c KP. Perrett, SA. Halperin, T. Nolan, C. Martínez Pancorbo, B. Tapiero, F. Martinón-Torres, Z. Stranak, M. Virta, OG. Vanderkooi, P. Kosina, MB. Encinas Pardilla, I. Cristobal García, GV. Zuccotti, L. Kostanyan, N. Meyer, MA. Ceregido, B. Cheuvart, SO. Kuriyakose, M. Marcos Fernández, MÁ. Rodríguez Zambrano, A. Martín García, JE. Asenjo de la Fuente, MD. Camacho Marín, M. de la Calle Fernández-Miranda, Y. Romero Espinar, PG. Marchisio, P. Manzoni, N. Mesaros

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$a BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.

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$a Halperin, Scott A $u Dalhousie University, Canadian Center for Vaccinology, Halifax, Canada. Electronic address: scott.halperin@dal.ca

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$a Nolan, Terry $u Murdoch Children's Research Institute and Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. Electronic address: t.nolan@unimelb.edu.au

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$a Martínez Pancorbo, Cristina $u Instituto Sevillano de la Mujer-Instituto Hispalense de Pediatría, Seville, Spain

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$a Tapiero, Bruce $u CHU Sainte Justine, Université de Montréal, Montréal, Canada. Electronic address: b.tapiero@umontreal.ca

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$a Martinón-Torres, Federico $u Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela and Genetics, Vaccines and Pediatrics Research Group, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: federico.martinon.torres@sergas.es

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$a Stranak, Zbynek $u Institute for the Care of Mother and Child, Prague, Czech Republic. Electronic address: z.stranak@seznam.cz

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$a Virta, Miia $u Tampere Vaccine Research Center, Tampere University, Tampere, Finland. Electronic address: miia.virta@staff.uta.fi

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$a Vanderkooi, Otto G $u Alberta Children's Hospital, University of Calgary, Alberta, Calgary, Canada. Electronic address: ovanderk@ucalgary.ca

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$a Encinas Pardilla, Maria Begoña $u Hospital Universitario Puerta de Hierro, Majadahonda, Spain

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$a Cristobal García, Ignacio $u Universidad Francisco de Vitoria, Madrid, Spain. Electronic address: icristobalg@sego.es

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$a Zuccotti, Gian Vincenzo $u Ospedale dei Bambini Vittore Buzzi and University of Milan, Milan, Italy. Electronic address: gianvincenzo.zuccotti@unimi.it

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$a Kostanyan, Lusine $u Modis, C/O GSK, Wavre, Belgium. Electronic address: lusine.x.kostanyan@gsk.com

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$a Meyer, Nadia $u GSK, Wavre, Belgium. Electronic address: nadia.x.meyer@gsk.com

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$a Ceregido, Maria Angeles $u GSK, Wavre, Belgium. Electronic address: maria-angeles.x.ceregido@gsk.com

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$a Cheuvart, Brigitte $u GSK, Wavre, Belgium. Electronic address: brigitte.cheuvart@gsk.com

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$a Marcos Fernández, Manuel $u Hospital Monteprincipe, Boadilla del Monte, Spain. Electronic address: mmarcos@egom.es

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$a Martín García, Adrián $u Nuevo Hospital Universitario de Burgos, Burgos, Spain

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$a Asenjo de la Fuente, Juan Eloy $u Hospital Clínico San Carlos, Madrid, Spain. Electronic address: eloyasenjo@telefonica.net

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$a Camacho Marín, Maria Dolores $u Hospital Clínico San Carlos, Madrid, Spain

700    1_

$a de la Calle Fernández-Miranda, María $u Hospital La Paz, Madrid, Spain

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$a Romero Espinar, Yolanda $u Hospital Quirónsalud Málaga, Málaga, Spain

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$a Marchisio, Paola Giovanna $u Università degli Studi di Milano, Milan, Italy. Electronic address: paola.marchisio@unimi.it

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$a Manzoni, Paolo $u Ospedale Ostetrico Ginecologico Sant'Anna, Turin, Italy and Department of Maternal-Infant-Pediatric Health, Degli Infermi Hospital, Biella, Italy

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$a Mesaros, Narcisa $u GSK, Wavre, Belgium. Electronic address: narcisa.x.mesaros@gsk.com

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