AEGiS-15IAC: Prophylactic DermaVir vaccination polarizes Th-1 type responses suppressing viral replication in rhesus macaques.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Prophylactic DermaVir vaccination polarizes Th-1 type responses suppressing viral replication in rhesus macaques.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1347)

Lisziewicz J, Trocio J, Whitman L, Ryder A, Bakare N, Markham P, Lisziewicz Z, Panicali D, Lifson J, Sampa S, Letvin N, Lori F
Genetic Immunity, LLC and Research Institute for Genetic and Human Therapy, Washington, DC, USA, Washington, DC, United States

BACKGROUND: DermaVir is a novel topical DNA vaccine expressing structural and regulatory gene products in dendritic cells (DC) that polarize naïve T cells towards a Th1 response. Based on data showing that DermaVir therapeutic immunization induced T-cell mediated immune responses and inhibited viral load rebound in chronically SIV[251]-infected rhesus macaques, clinical trials will be initiated in both HIV-infected adults and children.

METHODS: Here we investigated the immunogenicity and antiviral activity of prophylactic DermaVir[SHIV] in 16 naïve rhesus macaques randomized as: (1) untreated controls, (2) 5 doses of topical DermaVir (0.1 mg DNA/dose), (3) 5 doses of ex vivo DermaVir-treated DC (0.004mg DNA/dose), and (4) same as #3 with 1 MVA (SHIV 89.6p gag/env) boost. Immune responses to viral proteins were evaluated by ELISpot and intracellular cytokine (ICC) assays, delayed type hypersensitivity (DTH) skin test and antibodies by ELISA before and after SHIV 89.6p i.v. challenge.

RESULTS: Prior to challenge both ex vivo and topical DermaVir vaccinations induced T cell mediated immune responses measured by ICC and DTH assays, but no detectable viral antibodies. MVA boosted vigorous T cell responses and low levels of antibodies confirming the Th-1-polarized DermaVir priming. After challenge, all vaccinated animals showed a rapid anamnestic response characterized with robust T cell-mediated immune responses and high titers of virus-specific antibodies. Median viral loads in all vaccinated groups were significantly lower than in the control group. The most effective suppression of virus replication was observed in the MVA-boosted group where the viral load in 75% of the animals was suppressed to undetectable levels and no animal lost CD4.

CONCLUSIONS: This is the first example that cellular immunity in the absence of antibodies can suppress viral replication, reminiscent of the African sex workers case, however, boosting can broaden the response and enhance protection.

Keywords: AEGIS, Macaca mulatta, SIV, Vaccination, Simian Acquired Immunodeficiency Syndrome, Virus Replication, Vaccines, DNA, Viral Load, Genes, gag, HIV Antibodies, HIV, Genes, env, Immunization, Acquired Immunodeficiency Syndrome, HIV Infections, Animal, Adult, Child, virology, immunology, genetics

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ThOrA1347