No reactivation of attenuated immunodeficiency viruses in rhesus macaques after vaccinia virus-induced immune activation.

Abstract

Live-attenuated simian immunodeficiency virus (SIV) protects macaques against challenge with pathogenic SIV. To evaluate the safety of such vaccines, an investigation of whether or not nefdeleted SIV could be reactivated in vivo by immune activation of the host was conducted. In addition, monkeys infected with apathogenic SIV/HIV-1 chimeric viruses, and two control monkeys that had suppressed replication of pathogenic SIV were examined. During the infection virus became undetectable or persisted at a low level of replication in all monkeys. At this time-point 11 monkeys were immune-activated by a vaccinia virus (VV) superinfection. After VV infection up to 80 % of their lymphocytes showed expression of the activation markers CD25 and CD69 over 2 weeks. However, only the two non-progressing monkeys infected with pathogenic SIV showed a noticeable but transient enhancement of SIV replication and increased SIV antibody titres. By contrast, in monkeys infected with apathogenic immunodeficiency viruses no change in virus load was observed. Therefore, attenuated immunodeficiency viruses cannot be reactivated in vivo by a VV-induced immune activation.In recent years several vaccination strategies against human immunodeficiency virus (HIV) have been evaluated in the simian immunodeficiency virus (SIV) model for AIDS. By far the most successful vaccines are those based on live-attenuated SIV. These attenuated viruses have a reduced pathogenicity caused primarily by their low replicative capacity in the host.

Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses

“…Immunization with nonpathogenic SHIV89.6 led to the induction of persistent anti-SIV proliferative responses in the majority of animals, as has been observed after immunization with live attenuated viruses (19). In the present study, SHIV89.6-vaccinated animals were able to maintain SIV-specific proliferative responses during the acute p.c.…”

Long-Lasting Protection by Live Attenuated Simian Immunodeficiency Virus in Cynomolgus Monkeys: No Detection of Reactivation after Stimulation with a Recall Antigen

“…In monkey A91, as already observed in HIVinfected patients (Oprail et al, 1991), the severity of the immune deficit correlated with the absence of TT response and with detectable variations of the number of SIV proviral copies. Similar findings have been observed after vaccinia virus superinfection of monkeys infected with live attenuated virus but not exposed to any challenge virus (Dittmer et al, 1997). Based on a comparison of the data on the proliferative responses observed in naive monkeys with those derived from vaccinated and control infected monkeys before the TT boosters, it seems that the failure to detect proliferative responses is not dependent on the SIV infection per se.…”