Therapeutic immunization with Modified Vaccinia Virus Ankara (MVA) vaccines in SIV-infected rhesus monkeys undergoing antiretroviral therapy

Abstract

The long-term benefits of highly active antiretroviral therapy in HIV-infected patients are limited by emergence of drug-resistant variants and side effects. Therefore, we studied the concept of therapeutic immunization in 18 rhesus monkeys infected with a highly pathogenic simian immunodeficiency virus (SIV) swarm. Monkeys were treated with the reverse transcriptase inhibitor (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for 19 weeks starting 10 days after infection. After suppression of viremia, one group of monkeys was immunized with recombinant modified vaccinia virus Ankara (MVA) vectors expressing gag-pol and env. A second group received MVA vectors expressing the regulatory genes tat, rev and nef, while a third group was not immunized. Immunization with gag-pol and env expressing MVA enhanced SIV antibody titers. Following discontinuation of PMPA treatment, a rebound in viral load was observed. However, in three of six monkeys immunized with MVA gag-pol and MVA env, and two of six monkeys immunized MVA expressing regulatory genes set point RNA levels were below or close to a threshold level of 10(4) RNA copies/ml, while only one of six unvaccinated monkeys maintained such low RNA levels. Although a subset of animals seem to benefit from therapeutic immunization with MVA vectors, the difference in set point RNA levels between the groups did not reach statistical significance.