OA16.03
Background: Among the HIV-vaccine strategies tested to date, those involving recombinant viral vectors with ongoing replication such as those from the Herpesvirus family show the most promise. We have taken advantage of a well-studied virus, Varicella Zoster Virus (VZV), as a vector for HIV antigens and anticipate the induction of a durable and multifaceted immune response against HIV when adopting this approach. VZV establishes a latent infection with cycles of sub-clinical reactivation that can potentially boost the immune response against HIV antigens throughout life; an advantage over prime-boosting schemes against HIV.
Methods: We have recently utilized VZV as an SIV vaccine vector in the cynomolgus macaque model of HIV and demonstrated that approximately 33% of the animals vaccinated a single time with a VZV-SIV construct and challenged intra-rectally with multi low-dose SIV, controlled SIV viral load down to undetectable levels after initial infection. In addition, the remaining vaccines maintained their set-point viral loads significantly lower than controls (p<0.001). Immune responses associated with viral control have been assessed by multi-parameter flow cytometry in various tissues including blood, rectal tissue, lymph nodes and broncho-alveolar sites.
Results: Analysis of the systemic immune response showed the presence of a pool of TEM cells that correlated to a reduction in the set-point viral load (p<0.001). We also have found evidence that Th17 response in the gut and lymph nodes may play an important role in the control of viral load (p<0.05). We are currently investigating the dynamics between different T cell populations (TEM, Tregs, Th17 and Th22) as well as immune activation longitudinally during the infection phase of this trial with emphasis on the interplay between blood and mucosa.
Conclusions: The sustained viral clearance observed in this study offers an exciting platform to investigate possible immune correlates of protection against SIV.
