Citron Michael P, McAnulty Jessica, Callahan Cheryl, Knapp Walter, Fontenot Jane, Morales Pablo, Flynn Jessica A, Douglas Cameron M, Espeseth Amy S
Infectious Disease & Vaccines, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Safety Assessment and Laboratory Animal Resources, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Pathogens. 2021 Nov 5;10(11):1441. doi: 10.3390/pathogens10111441.
One approach to protect new-borns against respiratory syncytial virus (RSV) is to vaccinate pregnant women in the last trimester of pregnancy. The boosting of circulating antibodies which can be transferred to the foetus would offer immune protection against the virus and ultimately the disease. Since non-human primates (NHPs) have similar reproductive anatomy, physiology, and antibody architecture and kinetics to humans, we utilized this preclinical species to evaluate maternal immunization (MI) using an RSV F subunit vaccine. Three species of NHPs known for their ability to be infected with human RSV in experimental challenge studies were tested for RSV-specific antibodies. African green monkeys had the highest overall antibody levels of the old-world monkeys evaluated and they gave birth to offspring with anti-RSV titers that were proportional to their mother. These higher overall antibody levels are associated with greater durability found in their offspring. Immunization of RSV seropositive AGMs during late pregnancy boosts RSV titers, which consequentially results in significantly higher titers in the vaccinated new-borns compared to the new-borns of unvaccinated mothers. These findings, accomplished in small treatment group sizes, demonstrate a model that provides an efficient, resource sparing and translatable preclinical in vivo system for evaluating vaccine candidates for maternal immunization.
一种保护新生儿免受呼吸道合胞病毒（RSV）感染的方法是在妊娠晚期为孕妇接种疫苗。增强可转移至胎儿的循环抗体，将为胎儿提供针对该病毒及最终针对该疾病的免疫保护。由于非人灵长类动物（NHPs）在生殖解剖学、生理学以及抗体结构和动力学方面与人类相似，我们利用这种临床前动物模型，使用RSV F亚基疫苗评估母体免疫（MI）。在实验性攻毒研究中，对三种已知能够感染人RSV的非人灵长类动物进行了RSV特异性抗体检测。在接受评估的旧世界猴中，非洲绿猴的总体抗体水平最高，它们所生后代的抗RSV滴度与母亲的滴度成正比。这些较高的总体抗体水平与在其后代中发现的更强的抗体持久性相关。在妊娠晚期对RSV血清阳性的非洲绿猴进行免疫接种可提高RSV滴度，因此与未接种疫苗母亲所生的新生儿相比，接种疫苗的新生儿体内的滴度显著更高。这些在小规模治疗组中取得的研究结果，展示了一个可为评估母体免疫候选疫苗提供高效、节省资源且可转化的临床前体内系统的模型。
