Therapeutic immunization with Modified Vaccinia Virus Ankara (MVA) vaccines in SIV-infected rhesus monkeys undergoing antiretroviral therapy.
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 10(4) 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.
Uberla
Klaus
K
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany. klaus.ueberla@ruhr-uni-bochum.de
Rosenwirth
Brigitte
B
Ten Haaft
Peter
P
Heeney
Jonathan
J
Sutter
Gerd
G
Erfle
Volker
V
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D015685:Fusion Proteins, gag-pol / Q000276:immunology; D005822:Genetic Vectors; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D063065:Organophosphonates / Q000627:therapeutic use; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D000068698:Tenofovir; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics
D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral; D015685:Fusion Proteins, gag-pol; D063065:Organophosphonates; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D000068698:Tenofovir; D000225:Adenine