A Randomized Phase 4 Study of Immunogenicity and Safety After Monovalent Oral Type 2 Sabin Poliovirus Vaccine Challenge in Children Vaccinated with Inactivated Poliovirus Vaccine in Lithuania.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
04 01 2021
Historique:
received: 14 04 2020
accepted: 25 06 2020
pubmed: 6 7 2020
medline: 11 6 2021
entrez: 5 7 2020
Statut: ppublish

Résumé

Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)-immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks. In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination. After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%-62%) were shedding virus; 9 of 37 (24%; 12%-41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported. High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus.

Sections du résumé

BACKGROUND
Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)-immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks.
METHODS
In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination.
RESULTS
After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%-62%) were shedding virus; 9 of 37 (24%; 12%-41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported.
CONCLUSIONS
High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus.

Identifiants

pubmed: 32621741
pii: 5867494
doi: 10.1093/infdis/jiaa390
pmc: PMC7781454
doi:

Substances chimiques

Antibodies, Neutralizing 0
Poliovirus Vaccine, Inactivated 0
Poliovirus Vaccine, Oral 0

Banques de données

ClinicalTrials.gov
['NCT02582255']

Types de publication

Clinical Trial, Phase IV Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

119-127

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Ananda S Bandyopadhyay (AS)

Bill & Melinda Gates Foundation, Seattle, Washington, USA.

Chris Gast (C)

Biostatistical Consulting, Washington, USA.

Elizabeth B Brickley (EB)

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Ricardo Rüttimann (R)

Fighting Infectious Diseases in Emerging Countries, Miami, Florida, USA.

Ralf Clemens (R)

Global Research in Infectious Diseases, Rio de Janeiro, Brazil.

M Steven Oberste (MS)

Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

William C Weldon (WC)

Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Margaret E Ackerman (ME)

Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.

Ruth I Connor (RI)

Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Wendy F Wieland-Alter (WF)

Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Peter Wright (P)

Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Vytautas Usonis (V)

Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Lithuania.

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Classifications MeSH