Evaluation of recombinant respiratory syncytial virus gene deletion mutants in African green monkeys for their potential as live attenuated vaccine candidates

摘要

Towards the goal of developing live attenuated respiratory syncytial virus (RSV) vaccines to prevent severe respiratory tract infections caused by respiratory syncytial virus, recombinant RSV containing a deletion of single or multiple NS1, NS2, SH and M2-2 genes have been generated. In this study, recombinants, rA2DeltaM2-2, rA2DeltaNS2, rA2DeltaNS1NS2, rA2DeltaSHNS2, rA2DeltaM2-2NS2 were evaluated in African green monkeys (AGMs) for their infectivity, immunogenicity and protection against wild type (wt) RSV challenge. Replication of rA2DeltaNS2 and rA2DeltaSHNS2 was not attenuated in either the upper or the lower respiratory tracts of AGMs. On the other hands, rA2DeltaNS1NS2 was over-attenuated; it did not replicate in the respiratory tracts of the infected monkeys and did not provide sufficient protection against wild type RSV challenge. rA2DeltaM2-2NS2 was slightly more attenuated than rA2DeltaM2-2 and provided partial protection against wt RSV challenge. rA2DeltaM2-2, and possibly rA2DeltaM2-2NS2, exhibited the attenuated but protective phenotypes in the monkeys that could be further evaluated as potential live attenuated RSV vaccine candidates in the clinical studies.