A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains

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Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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@article{bccab9082d6b41da950af0362b8692a7,

title = "A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains",

abstract = "Maternal vaccination is a promising strategy for preventing neonatal disease caused by group B Streptococcus. The safety and immunogenicity of the prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like proteins (Alp) αC and Rib, were recently evaluated favorably in healthy adult women in a phase 1 trial. Here we demonstrate robust immunoglobulin G (IgG) and immunoglobulin A (IgA) responses against αC and Rib, as well as against the heterotypic Alp family members Alp1-Alp3. IgA and heterotypic IgG responses are more variable between subjects and correlate with pre-existing immunity. Vaccine-induced IgG mediates opsonophagocytic killing and prevents bacterial invasion of epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the vaccine domains is dominated by IgG1. Consistent with the high IgG1 cross-placental transfer rate, naturally acquired IgG against both domains reaches higher concentrations in neonatal than maternal blood, as assessed in a separate group of non-vaccinated pregnant women and their babies.",

keywords = "Adult, Female, Humans, Immunoglobulin A, Immunoglobulin G, Infant, Infant, Newborn, Placenta, Pregnancy, Protein Subunits, Streptococcus agalactiae, Vaccines, Subunit",

author = "Andrzej Pawlowski and Jonas Lannerg{\aa}rd and Majela Gonzalez-Miro and Duojia Cao and Sara Larsson and Persson, {Jenny J} and Geoff Kitson and Michael Darsley and Rom, {Ane Lille{\o}re} and Morten Hedegaard and Fischer, {Per B} and Bengt Johansson-Lindbom",

note = "{\textcopyright} 2022 The Author(s).",

year = "2022",

month = feb,

day = "15",

doi = "10.1016/j.xcrm.2022.100511",

language = "English",

volume = "3",

pages = "100511",

journal = "Cell reports. Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "2",

}

RIS

TY - JOUR

T1 - A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains

AU - Pawlowski, Andrzej

AU - Lannergård, Jonas

AU - Gonzalez-Miro, Majela

AU - Cao, Duojia

AU - Larsson, Sara

AU - Persson, Jenny J

AU - Kitson, Geoff

AU - Darsley, Michael

AU - Rom, Ane Lilleøre

AU - Hedegaard, Morten

AU - Fischer, Per B

AU - Johansson-Lindbom, Bengt

PY - 2022/2/15

Y1 - 2022/2/15

N2 - Maternal vaccination is a promising strategy for preventing neonatal disease caused by group B Streptococcus. The safety and immunogenicity of the prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like proteins (Alp) αC and Rib, were recently evaluated favorably in healthy adult women in a phase 1 trial. Here we demonstrate robust immunoglobulin G (IgG) and immunoglobulin A (IgA) responses against αC and Rib, as well as against the heterotypic Alp family members Alp1-Alp3. IgA and heterotypic IgG responses are more variable between subjects and correlate with pre-existing immunity. Vaccine-induced IgG mediates opsonophagocytic killing and prevents bacterial invasion of epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the vaccine domains is dominated by IgG1. Consistent with the high IgG1 cross-placental transfer rate, naturally acquired IgG against both domains reaches higher concentrations in neonatal than maternal blood, as assessed in a separate group of non-vaccinated pregnant women and their babies.

AB - Maternal vaccination is a promising strategy for preventing neonatal disease caused by group B Streptococcus. The safety and immunogenicity of the prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like proteins (Alp) αC and Rib, were recently evaluated favorably in healthy adult women in a phase 1 trial. Here we demonstrate robust immunoglobulin G (IgG) and immunoglobulin A (IgA) responses against αC and Rib, as well as against the heterotypic Alp family members Alp1-Alp3. IgA and heterotypic IgG responses are more variable between subjects and correlate with pre-existing immunity. Vaccine-induced IgG mediates opsonophagocytic killing and prevents bacterial invasion of epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the vaccine domains is dominated by IgG1. Consistent with the high IgG1 cross-placental transfer rate, naturally acquired IgG against both domains reaches higher concentrations in neonatal than maternal blood, as assessed in a separate group of non-vaccinated pregnant women and their babies.

KW - Adult

KW - Female

KW - Humans

KW - Immunoglobulin A

KW - Immunoglobulin G

KW - Infant

KW - Infant, Newborn

KW - Placenta

KW - Pregnancy

KW - Protein Subunits

KW - Streptococcus agalactiae

KW - Vaccines, Subunit

UR - http://www.scopus.com/inward/record.url?scp=85124518199&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2022.100511

DO - 10.1016/j.xcrm.2022.100511

M3 - Journal article

C2 - 35243418

VL - 3

SP - 100511

JO - Cell reports. Medicine

JF - Cell reports. Medicine

SN - 2666-3791

IS - 2

M1 - 100511

ER -

ID: 77931896

A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains

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