Adeno-Associated Virus as an Effective Malaria Booster Vaccine Following Adenovirus Priming.

摘要: An ideal malaria vaccine platform should potently induce protective immune responses and block parasite transmission from mosquito to human, it maintain these effects for an extended period. Here, we have focused on development based adeno-associated virus serotype 1 (AAV1), a viral vector widely studied in the field of clinical gene therapy that is able long-term transgene expression without causing toxicity vivo. Our results show potential utility AAV1 vectors as extremely potent booster durable immunity when combined with adenovirus-priming rodent model. We generated series recombinant AAV1s human adenovirus type 5 (AdHu5) expressing either Plasmodium falciparum circumsporozoite protein (PfCSP) or P25 (Pfs25) protein. Heterologous two-dose immunization AdHu5-prime AAV1-boost (AdHu5-AAV1) elicited robust PfCSP- Pfs25-specific functional antibodies over 280 days. Regarding efficacy, AdHu5-AAV1 PfCSP achieved high sterile protection (up 80% rate) against challenge transgenic berghei sporozoites PfCSP. When examining transmission-blocking (TB) found Pfs25 maintained TB activity vivo P. 287 days (99% reduction oocyst intensity, 85% prevalence). data indicate AAV1-based vaccines can confer well efficacy administered following AdHu5 priming vaccine, supporting further evaluation this regimen trials next-generation platform.