Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

• DOI: 10.1016/j.vaccine.2004.03.009
• Publication Date: 2004-04-09T09:21:57Z
• Authors: Maria Teresa Magg...; Silvia Baroncelli; Zuleika Michelini; Emanuele Fanales-...; Sonia Moretti; Leonardo Sernicola; Andrea Cara; Donatella R.M Negri; Stefano Buttò; Valeria Fiorelli; Antonella Tripiciano; Arianna Scoglio; Antonella Caputo; Alessandra Borsetti; Barbara Ridolfi; Roberta Bona; Peter ten Haaft; Iole Macchia; Pasqualina Leone; Maria Rosaria Pav...; Filomena Nappi; Massimo Ciccozzi; Jonathan Heeney; Fausto Titti; Aurelio Cafaro; Barbara Ensoli
• Keywords: AIDS Vaccines; CD4-Positive T-Lymphocytes; Male; 0301 basic medicine; B-Lymphocytes; Vaccination; Simian Acquired Immunodeficiency Syndrome; Gene Products, env; Gene Products, gag; CD8-Positive T-Lymphocytes; Recombinant Proteins; 3. Good health; HIV vaccine; Macaca fascicularis; Tat; Molecular Medicine; Immunology and Microbiology (all); Veterinary (all); Public Health, Environmental and Occupational Health; Infectious Diseases; Interferon-gamma; Macaca fascicularis; 03 medical and health sciences; DNA, Viral; Gene Products, tat; HIV-1; Animals; Humans; RNA, Viral; Simian Immunodeficiency Virus; Lymph Nodes

Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.