Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys.
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.
Maggiorella
Maria Teresa
MT
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Baroncelli
Silvia
S
Michelini
Zuleika
Z
Fanales-Belasio
Emanuele
E
Moretti
Sonia
S
Sernicola
Leonardo
L
Cara
Andrea
A
Negri
Donatella R M
DR
Buttò
Stefano
S
Fiorelli
Valeria
V
Tripiciano
Antonella
A
Scoglio
Arianna
A
Caputo
Antonella
A
Borsetti
Alessandra
A
Ridolfi
Barbara
B
Bona
Roberta
R
ten Haaft
Peter
P
Macchia
Iole
I
Leone
Pasqualina
P
Pavone-Cossut
Maria Rosaria
MR
Nappi
Filomena
F
Ciccozzi
Massimo
M
Heeney
Jonathan
J
Titti
Fausto
F
Cafaro
Aurelio
A
Ensoli
Barbara
B
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000096:biosynthesis / Q000276:immunology; D015686:Gene Products, env / Q000032:analysis / Q000096:biosynthesis; D015683:Gene Products, gag / Q000032:analysis / Q000096:biosynthesis; D015696:Gene Products, tat / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D012367:RNA, Viral / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D014611:Vaccination; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004279:DNA, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015686:Gene Products, env; D015683:Gene Products, gag; D015696:Gene Products, tat; D012367:RNA, Viral; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma