K. K. A. Van Rompay

Immediate zidovudine treatment protects simian immunodeficiency virus-infected newborn macaques against rapid onset of AIDS.

Simian immunodeficiency virus (SIV) infection of newborn rhesus macaques is a practical animal model of pediatric AIDS. Intravenous inoculation of rhesus newborns with uncloned SIVmac resulted in a high virus load, no antiviral immune responses, severe immunodeficiency, and a high mortality rate within 3 months. In contrast, immediate oral zidovudine (AZT) treatment of SIV-inoculated rhesus newborns either prevented infection or resulted in reduced virus load, enhanced antiviral immune responses, a low frequency of AZT-resistant virus isolates, and delayed disease progression with negligible toxicity. These results suggest that early chronic AZT treatment of human immunodeficiency virus-exposed newborns may have benefits that outweigh its potential side effects.

A recombinant attenuated Mycobacterium tuberculosis-SIV combination vaccine is safe and immunogenic in immunocompromised, SIV-infected infant macaques

Author(s): Jensen, K; Ranganathan, UD; Kozlowski, P; Van Rompay, K; Canfield, D; Ravindran, R; Khan, I; Luciw, P; Fennelly, G; Larsen, M; Abel, K

P14-08. Intramuscular DNA delivery by electroporation leads to greatly enhanced systemic and mucosal immune responses and control of SIVmac251 challenge

Results DNA delivery using EP led to greatly enhanced expression of SIV antigens and increased cellular responses (up 3% of total T cells) that were broad, long-lasting (up to 45 weeks post vaccination) and included cells of multifunctional phenotype. SIV-specific cellular responses were found both in blood, BAL and rectal mucosa. Interestingly, compared to blood, the responses in BAL were consistently higher (up to 2 log) and included a higher frequency of polyfunctional cells. The cellular responses were characterized as predominantly EM CD4+ and CD8+ T cells in BAL and as both CM and EM T cells in blood. EP DNA delivery elicited both systemic and mucosal humoral immune responses, including the induction of Gag-specific IgA. Upon high dose SIVmac251 challenge, the vaccinated animals showed statistically significant lower VL peak in acute (1 log10) and in chronic viremia (1.7 log10).

P11-19. Altered mucosal distribution of SIV-specific T cells in Rhesus macaques infected with the live-attenuated Rev-independent SIV

Background Infection of rhesus macaques with live-attenuated SIV strains provides the best known protection against challenge with pathogenic SIV. A cohort of 10 Indian rhesus macaques infected by Rev-independent live-attenuated SIV was monitored for up to 10 years. After the initial acute phase, virus replication was controlled and plasma viral loads were persistently below the threshold of the assay. None of the animals showed any signs of immune dysfunction.