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The Maternal Group B Streptococcus Alpha-Like Protein Subunit Vaccine GBS-NN Targets Homotypic and Heterotypic Strains, Confers Opsonophagocytic Killing and Prevents in vitro Invasion of Human Epithelial Cells

Pawlowski, Andrzej LU ; Lannergård, Jonas LU ; Gonzalez-miro, Majela LU ; Cao, Duojia LU ; Larsson, Sara LU ; Persson, Jenny J. LU ; Kitsson, Geoff ; Darsley, Michael ; Rom, Ane Lilleøre and Hedegaard, Morten , et al. (2021) p.1-58
Abstract
Maternal vaccination, resulting in transfer of protective IgG across the placenta, represents a promising strategy to prevent neonatal disease caused by group B Streptococcus (GBS). The prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like protein (Alp) family members AlphaC and Rib, has been shown to display a good safety profile and to elicit a strong antibody response against the intact GBS-NN protein in a randomized placebo-controlled double-blind phase 1 trial in healthy adult women. Here we show that the vaccinees achieve robust IgG and IgA responses against both AlphaC and Rib and that vaccination additionally gives rise to antibodies against the heterotypic Alp family members Alp1-3.... (More)
Maternal vaccination, resulting in transfer of protective IgG across the placenta, represents a promising strategy to prevent neonatal disease caused by group B Streptococcus (GBS). The prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like protein (Alp) family members AlphaC and Rib, has been shown to display a good safety profile and to elicit a strong antibody response against the intact GBS-NN protein in a randomized placebo-controlled double-blind phase 1 trial in healthy adult women. Here we show that the vaccinees achieve robust IgG and IgA responses against both AlphaC and Rib and that vaccination additionally gives rise to antibodies against the heterotypic Alp family members Alp1-3. Responses against the heterotypic N-domains were more variable between subjects and correlated strongly with levels of pre-existing antibodies. Postvaccination sera mediated opsonophagocytic killing that correlated strongly with IgG but not IgM responses elicited by the vaccine. These sera also consistently prevented bacterial invasion of human cervical epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the N-domains of AlphaC and Rib was dominated by the IgG1 subclass. Consistent with the enhanced ability of IgG1 to cross the placenta, naturally acquired IgG against both domains accumulated in neonatal relative to maternal blood, as assessed in a separate group of non-vaccinated 
pregnant women and their babies. (Less)
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organization
publishing date
type
Working paper/Preprint
publication status
submitted
subject
pages
1 - 58
publisher
SSRN Sneak Peek
DOI
10.2139/ssrn.3924602
language
English
LU publication?
yes
id
b41f77bb-b1d9-4d7e-bddd-96910cff1b42
alternative location
https://www.ssrn.com/abstract=3924602
date added to LUP
2021-11-25 11:13:18
date last changed
2021-12-07 08:52:08
@misc{b41f77bb-b1d9-4d7e-bddd-96910cff1b42,
  abstract     = {{Maternal vaccination, resulting in transfer of protective IgG across the placenta, represents a promising strategy to prevent neonatal disease caused by group B Streptococcus (GBS). The prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like protein (Alp) family members AlphaC and Rib, has been shown to display a good safety profile and to elicit a strong antibody response against the intact GBS-NN protein in a randomized placebo-controlled double-blind phase 1 trial in healthy adult women. Here we show that the vaccinees achieve robust IgG and IgA responses against both AlphaC and Rib and that vaccination additionally gives rise to antibodies against the heterotypic Alp family members Alp1-3. Responses against the heterotypic N-domains were more variable between subjects and correlated strongly with levels of pre-existing antibodies. Postvaccination sera mediated opsonophagocytic killing that correlated strongly with IgG but not IgM responses elicited by the vaccine. These sera also consistently prevented bacterial invasion of human cervical epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the N-domains of AlphaC and Rib was dominated by the IgG1 subclass. Consistent with the enhanced ability of IgG1 to cross the placenta, naturally acquired IgG against both domains accumulated in neonatal relative to maternal blood, as assessed in a separate group of non-vaccinated 
pregnant women and their babies.}},
  author       = {{Pawlowski, Andrzej and Lannergård, Jonas and Gonzalez-miro, Majela and Cao, Duojia and Larsson, Sara and Persson, Jenny J. and Kitsson, Geoff and Darsley, Michael and Rom, Ane Lilleøre and Hedegaard, Morten and Fischer, Per and Johansson Lindbom, Bengt}},
  language     = {{eng}},
  note         = {{Preprint}},
  pages        = {{1--58}},
  publisher    = {{SSRN Sneak Peek}},
  title        = {{The Maternal Group B Streptococcus Alpha-Like Protein Subunit Vaccine GBS-NN Targets Homotypic and Heterotypic Strains, Confers Opsonophagocytic Killing and Prevents  <i>in vitro</i> Invasion of Human Epithelial Cells}},
  url          = {{http://dx.doi.org/10.2139/ssrn.3924602}},
  doi          = {{10.2139/ssrn.3924602}},
  year         = {{2021}},
}