Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Department of Global Health, University of Washington, Seattle, Washington, USA.
J Infect Dis. 2022 Aug 12;226(1):177-187. doi: 10.1093/infdis/jiac148.
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.
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.
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.
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.
B 群链球菌（GBS）在怀孕期间的传播可导致早产、死胎、胎儿损伤或新生儿感染。成人感染率也在上升。GBS-NN 疫苗通过融合 GBS Alpha C 和 Rib 蛋白的 N 端结构域而构建，在健康的非孕妇中是安全的，但在怀孕期间使用还需要进一步评估。在这里，我们使用模拟人类 GBS 感染结果的小鼠模型来测试 GBS-NN 疫苗的疗效。
在给予 GBS-NN 疫苗或佐剂后，通过 ELISA 比较抗体谱。通过比较 GBS-NN 疫苗接种组与佐剂对照组在全身和妊娠相关感染期间以及在母体疫苗接种后经鼻腔感染新生小鼠期间的感染结果，来检查疫苗的疗效。
与对照组相比，接种疫苗的小鼠具有更高的 GBS-NN 特异性 IgG 滴度。这些抗体结合了 GBS 临床分离株上的 Alpha C 和 Rib。从全身挑战接种疫苗的小鼠中回收的 GBS 较少。尽管疫苗接种并不能消除妊娠期间上行感染中的 GBS，但接种疫苗的母鼠经历的宫内胎儿死亡较少。此外，母体疫苗接种延长了经鼻腔 GBS 挑战后新生儿的存活时间。
这些发现表明 GBS-NN 疫苗在小鼠全身和围产期 GBS 感染中的疗效，并表明母体疫苗接种有助于将保护性抗体转移给新生儿。
