Safety, tolerability, and immunogenicity of inactivated poliovirus vaccine with or without E.coli double mutant heat-labile toxin (dmLT) adjuvant in healthy adults; a phase 1 randomized study

被引：5

作者：

Erdem, Rahsan ^{[1
]}

De Coster, Ilse ^{[2
]}

Withanage, Kanchanamala ^{[2
]}

Mercer, Laina D. ^{[1
]}

Marchant, Arnaud ^{[3
]}

Taton, Martin ^{[3
]}

Cools, Nathalie ^{[4
]}

Lion, Eva ^{[4
]}

Cassels, Fred ^{[1
]}

Higgins, Deborah ^{[1
]}

Ivinson, Karen ^{[1
]}

Locke, Emily ^{[1
]}

Mahmood, Kutub ^{[1
]}

Wright, Peter F. ^{[5
]}

Gast, Chris ^{[1
]}

White, Jessica A. ^{[1
]}

Ackerman, Margaret E. ^{[5
]}

Konopka-Anstadt, Jennifer L. ^{[6
]}

Mainou, Bernardo A. ^{[6
]}

Van Damme, Pierre ^{[2
]}

机构：

[1] Ctr Vaccine Innovat & Access, PATH, Seattle, WA USA

[2] Univ Antwerp, Vaccine & Infect Dis Inst, Ctr Evaluat Vaccinat, Campus Drie Eiken,Bldg Vaccinopolis,Drie Eikenstr, B-2650 Edegem, Belgium

[3] Univ libre Bruxelles, Inst Med Immunol, Brussels, Belgium

[4] Univ Antwerp, Vaccine & Infect Dis Inst, Lab Expt Hematol, Antwerp, Belgium

[5] Dartmouth Coll, Lebanon, NH USA

[6] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA

来源：

VACCINE | 2023年 / 41卷 / 10期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

Poliovirus; vaccine; inactivated poliovirus vaccine (IPV); dmLT; intestinal immunity; ANTIBODY-RESPONSES; IPV-AL; WORLDWIDE; IMMUNITY;

D O I：

10.1016/j.vaccine.2023.01.048

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Inactivated trivalent poliovirus vaccine (IPV) induces humoral immunity, which protects against paralytic poliomyelitis but does not induce sufficient mucosal immunity to block intestinal infection. We assessed the intestinal immunity in healthy adults in Belgium conferred by a co-formulation of IPV with the mucosal adjuvant double mutant Labile Toxin (dmLT) derived from Escherichia coli.Methods: Healthy fully IPV-vaccinated 18-45-year-olds were randomly allocated to three groups: on Day 1 two groups received one full dose of IPV (n = 30) or IPV + dmLT (n = 30) in a blinded manner, and the third received an open-label dose of bivalent live oral polio vaccine (bOPV types 1 and 3, n = 20). All groups received a challenge dose of bOPV on Day 29. Participants reported solicited and unsolicited adverse events (AE) using study diaries. Mucosal immune responses were measured by fecal neutralization and IgA on Days 29 and 43, with fecal shedding of challenge viruses measured for 28 days. Humoral responses were measured by serum neutralizing antibody (NAb).Results: Solicited and unsolicited AEs were mainly mild-to-moderate and transient in all groups, with no meaningful differences in rates between groups. Fecal shedding of challenge viruses in both IPV groups exceeded that of the bOPV group but was not different between IPV and IPV + dmLT groups. High serum NAb responses were observed in both IPV groups, alongside modest levels of fecal neutralization and IgA. Conclusions: Addition of dmLT to IPV administered intramuscularly neither affected humoral nor intestinal immunity nor decreased fecal virus shedding following bOPV challenge. The tolerability of the dose of dmLT used in this study may allow higher doses to be investigated for impact on mucosal immunity.Registered on ClinicalTrials.gov - NCT04232943.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

引用

页码：1657 / 1667

页数：11

共 31 条

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