Susceptibility to SIV Infection After Adenoviral Vaccination in a Low Dose Rhesus Macaque Challenge Model

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Human adenovirus serotype-5 (HAdV-5) vaccination linked to increased HIV susceptibility.
• Hypothesized mechanism involves activated CD4+ T cells at mucosal sites.
• Previous studies showed AdV-vector vaccination increased T cell activation in macaques.

Purpose of the Study:

• To investigate if AdV-vector vaccination increases susceptibility to SIV infection in a macaque model.
• To examine vaccine-induced changes in mucosal CD4+ T cell activation.

Main Methods:

• Developed a proof-of-concept vaccination-challenge model in rhesus macaques.
• Vaccinated macaques with a simian AdV-7 (SAdV-7) vector encoding an irrelevant insert.
• Challenged vaccinated and placebo groups with escalating doses of SIVmac251.

Main Results:

• SAdV-7 vaccination did not induce detectable mucosal CD4+ T cell activation.
• No significant increase in SIV acquisition was observed in vaccinated macaques (5/10) versus placebo (3/10).

Conclusions:

• Results do not support increased SIV susceptibility due to this specific AdV-vector vaccination in this model.
• Further large-scale studies are needed to confirm trends and mechanisms of AdV-vector associated SIV/HIV acquisition.