Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 226, Issue 1, Pages 177-187Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiac148
Keywords
group B Streptococcus; Streptococcus agalactiae; vaccine; neonate; pregnancy; maternal vaccination; surface proteins; alpha-like proteins; Rib; intranasal infection
Categories
Funding
- National Institutes of Health (NIH) [R01AI145890, R01AI152268, R01AI133575]
- NIH [T32 AI007509, T32 AI055396]
- Seattle Children's Research Institute
- MinervaX A/S
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This study demonstrates the efficacy of the GBS-NN vaccine in murine systemic and perinatal GBS infections and suggests that maternal vaccination facilitates the transfer of protective antibodies to neonates.
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. Immunization of mice with the surface protein fusion vaccine known as GBS-NN raises antibodies that provide protection during systemic and pregnancy-associated group B streptococcal infections and promotes neonatal survival during intranasal group B streptococcal infection following maternal vaccination.
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