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A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
A Recombinant Alpha-Like Protein Subunit Vaccine (GBS-NN) Provides Protection in Murine Models of Group B
Alyssa Brokaw1,2, Shayla Nguyen1, Phoenicia Quach1
1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Insights
The Group B Streptococcus (GBS) vaccine, GBS-NN, shows efficacy in protecting mice against GBS infections. Maternal vaccination also transfers protective antibodies to neonates, enhancing their survival.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Group B Streptococcus (GBS) poses risks during pregnancy, causing preterm labor, stillbirths, and neonatal infections, with rising adult infection rates.
- The GBS-NN vaccine, targeting GBS Alpha C and Rib proteins, is safe in nonpregnant women but requires evaluation for use during pregnancy.
- Mouse models are utilized to assess GBS infection outcomes and vaccine efficacy relevant to human GBS disease.
Purpose of the Study:
- To evaluate the efficacy of the GBS-NN vaccine in mouse models of systemic and pregnancy-associated Group B Streptococcus infections.
- To determine if maternal vaccination with GBS-NN confers protection to neonates against GBS challenge.
Main Methods:
- Antibody responses (IgG titers) were measured by ELISA after GBS-NN vaccine or adjuvant administration.
- Vaccine efficacy was assessed by comparing GBS recovery in systemically infected mice and pregnancy-associated infection outcomes in vaccinated dams versus controls.
- Neonatal survival was evaluated after intranasal GBS challenge in offspring from vaccinated mothers.
Main Results:
- GBS-NN vaccination induced higher GBS-NN-specific IgG titers that recognized GBS surface proteins.
- Vaccinated mice showed reduced GBS burden during systemic infection and fewer in utero fetal deaths in pregnant dams.
- Maternal vaccination with GBS-NN improved neonatal survival following intranasal GBS challenge.
Conclusions:
- The GBS-NN vaccine demonstrates efficacy in preclinical models of GBS infection, including systemic and perinatal contexts.
- Maternal GBS-NN vaccination facilitates the transfer of protective antibodies to neonates, offering protection against GBS challenge.
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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