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

Authors :
Brokaw A
Nguyen S
Quach P
Orvis A
Furuta A
Johansson-Lindbom B
Fischer PB
Rajagopal L
Source :
The Journal of infectious diseases [J Infect Dis] 2022 Aug 12; Vol. 226 (1), pp. 177-187.
Publication Year :
2022

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.<br />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.<br />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.<br />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.<br />Competing Interests: Potential conflicts of interest. B. J.-L. reports personal fees and grants from MinervaX A/S during the conduct of the study. P. B. F. reports personal fees from MinervaX A/S during the conduct of the study, personal fees from MinervaX A/S outside this submitted work, and has patent applications relating to the use of GBS-NN as a vaccine candidate. All other authors report no potential conflicts.<br /> (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1537-6613
Volume :
226
Issue :
1
Database :
MEDLINE
Journal :
The Journal of infectious diseases
Publication Type :
Academic Journal
Accession number :
35429401
Full Text :
https://doi.org/10.1093/infdis/jiac148