A polyvalent Clade B virus-like particle HIV vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus Infection in macaques and primes for virus-amplified immunity.

Abstract

Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown only partial protection from HIV-1 infection in human trials. Oral Truvada (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not been evaluated in humans. We determined the efficacy of combining a DNA/virus-like particle (VLP) vaccine with partially effective intermittent PrEP in Indian rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at weeks 0 and 4), followed by intramuscular and intranasal inoculations of homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were infected after a median of four exposures; the mean peak plasma viral load (VL) was 3.9×10(7) vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one infected CBP RM had a reduced peak VL of 8.8×10(5) copies/ml. SHIV exposures during PrEP amplified Gag and Env antibody titers in protected RM. These results suggest that combining oral PrEP with HIV vaccines could enhance protection against HIV-1 infection.

• Authors: Ted M Ross, Lara E Pereira, Amara Luckay, Janet M McNicholl, J Gerardo García-Lerma, Walid Heneine, Hermancia S Eugene, Brooke R Pierce-Paul, Jining Zhang, R Michael Hendry, James M Smith
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 30 Issue 11 Pg. 1072-81 (Nov 2014) ISSN: 1931-8405 [Electronic] United States
• PMID: 24914761 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Antibodies, Viral
• Drug Combinations
• Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Organophosphorus Compounds
• SAIDS Vaccines
• Vaccines, DNA
• Vaccines, Virus-Like Particle
• Deoxycytidine

Topics

• Administration, Intranasal
• Administration, Oral
• Animals
• Anti-HIV Agents (administration & dosage)
• Antibodies, Viral (blood)
• Chemoprevention (methods)
• Combined Modality Therapy (methods)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Combinations
• Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Female
• HIV-1 (genetics, immunology)
• Injections, Intramuscular
• Macaca mulatta
• Male
• Organophosphorus Compounds (administration & dosage)
• Pre-Exposure Prophylaxis (methods)
• SAIDS Vaccines (administration & dosage, immunology)
• Simian Acquired Immunodeficiency Syndrome (immunology, prevention & control)
• Simian Immunodeficiency Virus (genetics, immunology)
• Treatment Outcome
• Vaccination (methods)
• Vaccines, DNA (administration & dosage, immunology)
• Vaccines, Virus-Like Particle (administration & dosage, immunology)
• Viral Load