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

Pawlowski, Andrzej LU ; Lannergård, Jonas LU ; Gonzalez-Miro, Majela LU ; Cao, Duojia LU ; Larsson, Sara LU ; Persson, Jenny J. LU ; Kitson, Geoff ; Darsley, Michael ; Rom, Ane Lilleøre and Hedegaard, Morten , et al. (2022) In Cell Reports Medicine 3(2).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antibodies, group B Streptococcus, maternal immunization, neonatal disease, opsonophagocytosis, vaccines
in
Cell Reports Medicine
volume
3
issue
2
article number
100511
publisher
Elsevier
external identifiers
  • pmid:35243418
  • scopus:85124518199
ISSN
2666-3791
DOI
10.1016/j.xcrm.2022.100511
language
English
LU publication?
yes
id
76eaa183-ef30-4e7e-8b6c-619951070e36
date added to LUP
2022-04-13 11:44:51
date last changed
2024-04-23 12:04:31
@article{76eaa183-ef30-4e7e-8b6c-619951070e36,
  abstract     = {{<p>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.</p>}},
  author       = {{Pawlowski, Andrzej and Lannergård, Jonas and Gonzalez-Miro, Majela and Cao, Duojia and Larsson, Sara and Persson, Jenny J. and Kitson, Geoff and Darsley, Michael and Rom, Ane Lilleøre and Hedegaard, Morten and Fischer, Per B. and Johansson-Lindbom, Bengt}},
  issn         = {{2666-3791}},
  keywords     = {{antibodies; group B Streptococcus; maternal immunization; neonatal disease; opsonophagocytosis; vaccines}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Elsevier}},
  series       = {{Cell Reports Medicine}},
  title        = {{A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains}},
  url          = {{http://dx.doi.org/10.1016/j.xcrm.2022.100511}},
  doi          = {{10.1016/j.xcrm.2022.100511}},
  volume       = {{3}},
  year         = {{2022}},
}