Vaccination of Macaques with Long-Standing SIVmac251 Infection Lowers the Viral Set Point After Cessation of Antiretroviral Therapy

• Published in: The Journal of immunology (1950) 2002-11, Vol.169 (9), p.5347-5357
• Main Authors: Tryniszewska, Elzbieta, Nacsa, Janos, Lewis, Mark G, Silvera, Peter, Montefiori, David, Venzon, David, Hel, Zdenek, Parks, Robyn Washington, Moniuszko, Marcin, Tartaglia, Jim, Smith, Kendall A, Franchini, Genoveffa
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Drug Therapy, Combination; Epitopes, T-Lymphocyte - immunology; Immunization Schedule; Interleukin-2 - administration & dosage; Interleukin-2 - therapeutic use; Macaca mulatta; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - immunology; Simian Acquired Immunodeficiency Syndrome - drug therapy; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - drug effects; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - physiology; Viremia - drug therapy; Viremia - immunology; Viremia - prevention & control; Virus Replication - drug effects; Virus Replication - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.9.5347

A cohort of rhesus macaques with long-standing SIVmac251 infection (> or =5 mo) was treated with continuous antiretroviral therapy (ART). A group of eight macaques was vaccinated with or without simultaneous administration of low dose IL-2 with the highly attenuated poxvirus vector (NYVAC) vaccine candidate expressing the SIVmac structural gag-pol-env (gpe) genes and a novel chimeric fusion protein derived from the rev-tat-nef (rtn) regulatory genes. Control groups consisted of mock-vaccinated macaques or animals treated only with IL-2. Vaccination significantly expanded both virus-specific CD4(+) and CD8(+) T cell responses, and IL-2 further increased the vaccine-induced response to an immunodominant Gag epitope. Following antiretroviral treatment interruption, the viral set point was significantly lower in vaccinated than in control macaques for at least 4 consecutive mo, and viral containment was inversely correlated with vaccine-induced, virus-specific CD4(+) and CD8(+) T cell responses. These data provide the proof of concept that therapeutic vaccination before cessation of ART may be a feasible approach in the clinical management of HIV-1 infection.