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A Recombinant Alpha-Like Protein Subunit Vaccine (GBS-NN) Provides Protection in Murine Models of Group B Streptococcus Infection

Brokaw, Alyssa ; Nguyen, Shayla ; Quach, Phoenicia ; Orvis, Austyn ; Furuta, Anna ; Johansson-Lindbom, Bengt LU ; Fischer, Per B. and Rajagopal, Lakshmi (2022) In The Journal of infectious diseases 226(1). p.177-187
Abstract

BACKGROUND: Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes. METHODS: Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated... (More)

BACKGROUND: Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes. METHODS: Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated infections, and during intranasal infection of neonatal mice following maternal vaccination. RESULTS: Vaccinated mice had higher GBS-NN-specific IgG titers versus controls. These antibodies bound alpha C and Rib on GBS clinical isolates. Fewer GBS were recovered from systemically challenged vaccinated mice versus controls. Although vaccination did not eliminate GBS during ascending infection in pregnancy, vaccinated dams experienced fewer in utero fetal deaths. Additionally, maternal vaccination prolonged neonatal survival following intranasal GBS challenge. CONCLUSIONS: These findings demonstrate GBS-NN vaccine efficacy in murine systemic and perinatal GBS infections and suggest that maternal vaccination facilitates the transfer of protective antibodies to neonates.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Streptococcus agalactiae, alpha-like proteins, group B Streptococcus, intranasal infection, maternal vaccination, neonate, pregnancy, Rib, surface proteins, vaccine
in
The Journal of infectious diseases
volume
226
issue
1
pages
11 pages
publisher
Oxford University Press
external identifiers
  • pmid:35429401
  • scopus:85136339218
ISSN
1537-6613
DOI
10.1093/infdis/jiac148
language
English
LU publication?
yes
id
dadb277c-17d3-4d82-bd61-1ef0c8e213ae
date added to LUP
2022-10-14 13:48:15
date last changed
2024-06-13 20:09:44
@article{dadb277c-17d3-4d82-bd61-1ef0c8e213ae,
  abstract     = {{<p>BACKGROUND: Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes. METHODS: Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated infections, and during intranasal infection of neonatal mice following maternal vaccination. RESULTS: Vaccinated mice had higher GBS-NN-specific IgG titers versus controls. These antibodies bound alpha C and Rib on GBS clinical isolates. Fewer GBS were recovered from systemically challenged vaccinated mice versus controls. Although vaccination did not eliminate GBS during ascending infection in pregnancy, vaccinated dams experienced fewer in utero fetal deaths. Additionally, maternal vaccination prolonged neonatal survival following intranasal GBS challenge. CONCLUSIONS: These findings demonstrate GBS-NN vaccine efficacy in murine systemic and perinatal GBS infections and suggest that maternal vaccination facilitates the transfer of protective antibodies to neonates.</p>}},
  author       = {{Brokaw, Alyssa and Nguyen, Shayla and Quach, Phoenicia and Orvis, Austyn and Furuta, Anna and Johansson-Lindbom, Bengt and Fischer, Per B. and Rajagopal, Lakshmi}},
  issn         = {{1537-6613}},
  keywords     = {{Streptococcus agalactiae; alpha-like proteins; group B Streptococcus; intranasal infection; maternal vaccination; neonate; pregnancy; Rib; surface proteins; vaccine}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{177--187}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of infectious diseases}},
  title        = {{A Recombinant Alpha-Like Protein Subunit Vaccine (GBS-NN) Provides Protection in Murine Models of Group B Streptococcus Infection}},
  url          = {{http://dx.doi.org/10.1093/infdis/jiac148}},
  doi          = {{10.1093/infdis/jiac148}},
  volume       = {{226}},
  year         = {{2022}},
}