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.
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Maria Teresa
MT
Maggiorella
Silvia
S
Baroncelli
Zuleika
Z
Michelini
Emanuele
E
Fanales-Belasio
Sonia
S
Moretti
Leonardo
L
Sernicola
Andrea
A
Cara
Donatella R M
DR
Negri
Stefano
S
Buttò
Valeria
V
Fiorelli
Antonella
A
Tripiciano
Arianna
A
Scoglio
Antonella
A
Caputo
Alessandra
A
Borsetti
Barbara
B
Ridolfi
Roberta
R
Bona
Peter
P
ten Haaft
Iole
I
Macchia
Pasqualina
P
Leone
Maria Rosaria
MR
Pavone-Cossut
Filomena
F
Nappi
Massimo
M
Ciccozzi
Jonathan
J
Heeney
Fausto
F
Titti
Aurelio
A
Cafaro
Barbara
B
Ensoli
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