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

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Abstract
Background  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.Methods  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.Results  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 104 RNA copies/ml, while only one of six unvaccinated monkeys maintained such low RNA levels.Conclusions  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.

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