Minimal Protective Antibody Titers Elicited in Sheep by RVFV MP-12 and arMP-12ΔNSm21/384 Vaccine Candidates

Abstract

The live attenuated Rift Valley Fever Virus (RVFV) vaccine candidates, RVFV MP-12, and the recombinant derivative, RVFV arMP-12ΔNSm21/384 (MP-12NSm-del), are among the most promising next-generation domestic ruminant vaccine candidates. While both vaccines consistently elicit protective neutralizing Antibodies (nAb) in domestic ruminants, the minimal protective antibody titer is unknown. Therefore, we conducted studies to determine the minimal protective nAb titers elicited in sheep by these vaccines using a mouse model. The approach involved the transfer of sera obtained from sheep vaccinated with the MP-12 and MP-12NSm-del vaccines to 6- to 8-week-old BALB/c mice. The sheep nAb titers ranged from 20 to 640 at the time of transfer. A blood sample was obtained from each mouse 24 hours post-transfer to determine the nAb titer 2 hours before challenging each animal with a lethal dose of virulent RVFV (strain ZH501). All challenged mice were observed daily for 21 days for morbidity and mortality. The lowest nAb titer that protected the animals was interpreted as an estimate of the minimal protective efficacy of the vaccine. The results indicated that nAb titers as low as 10 to 20 elicited by the MP-12 and MP-12NSm-del vaccine candidates in sheep 10 days post-vaccination afforded protection to the mice. However, the nAbs elicited in one sheep by MP-12 before day 10 post-vaccination and ranging in titer from < 5 to 40 only afforded protection to 3 out of 18 mice, and therefore suggested that innate and/or the cellular immune response were also needed for protection during early RVFV infection. The findings further support these RVFV candidate vaccines as potential veterinary vaccines for domestic ruminants and offer a promising BALB/c mouse RVFV challenge model as a surrogate for evaluating the protective nAb response elicited by RVFV vaccines.