Vaccination with Tat Toxoid Attenuates Disease in Simian/HIV-challenged Macaques

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2000 Mar 22

PMID 10725402

Citations 33

Authors

C D Pauza

P Trivedi

M Wallace

T J Ruckwardt

H Le Buanec

W Lu

B Bizzini

A Burny

D Zagury

R C Gallo

Affiliations

Soon will be listed here.

Abstract

The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo. We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-alpha, and chemokine receptor expression (CXCR4 and CCR5) on CD4(+) T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.

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References

Lu Y, Pauza C, Lu X, Montefiori D, Miller C . Rhesus macaques that become systemically infected with pathogenic SHIV 89.6-PD after intravenous, rectal, or vaginal inoculation and fail to make an antiviral antibody response rapidly develop AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 19(1):6-18. DOI: 10.1097/00042560-199809010-00002. View

Steger K, Waterman P, Pauza C . Acute effects of pathogenic simian-human immunodeficiency virus challenge on vaccine-induced cellular and humoral immune responses to Gag in rhesus macaques. J Virol. 1999; 73(3):1853-9. PMC: 104425. DOI: 10.1128/JVI.73.3.1853-1859.1999. View

Barillari G, Gendelman R, Gallo R, Ensoli B . The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proc Natl Acad Sci U S A. 1993; 90(17):7941-5. PMC: 47263. DOI: 10.1073/pnas.90.17.7941. View

van Baalen C, Pontesilli O, Huisman R, Geretti A, Klein M, de Wolf F . Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte frequencies inversely correlate with rapid progression to AIDS. J Gen Virol. 1997; 78 ( Pt 8):1913-8. DOI: 10.1099/0022-1317-78-8-1913. View

Re M, Furlini G, Vignoli M, Ramazzotti E, Roderigo G, De Rosa V . Effect of antibody to HIV-1 Tat protein on viral replication in vitro and progression of HIV-1 disease in vivo. J Acquir Immune Defic Syndr Hum Retrovirol. 1995; 10(4):408-16. DOI: 10.1097/00042560-199512000-00003. View

Viscidi R, Mayur K, Lederman H, Frankel A . Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1. Science. 1989; 246(4937):1606-8. DOI: 10.1126/science.2556795. View

Robinson H, Montefiori D, Johnson R, Manson K, Kalish M, Lifson J . Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nat Med. 1999; 5(5):526-34. DOI: 10.1038/8406. View

Zagury J, Sill A, Blattner W, Lachgar A, Le Buanec H, Richardson M . Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine. J Hum Virol. 1999; 1(4):282-92. View

Zagury D, Lachgar A, Chams V, Fall L, Bernard J, Zagury J . Interferon alpha and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS. Proc Natl Acad Sci U S A. 1998; 95(7):3851-6. PMC: 19926. DOI: 10.1073/pnas.95.7.3851. View

10.

COHEN S, Li C, Ding L, Cao Y, Pardee A, Shevach E . Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge. Proc Natl Acad Sci U S A. 1999; 96(19):10842-7. PMC: 17970. DOI: 10.1073/pnas.96.19.10842. View

11.

Collman R, Balliet J, Gregory S, Friedman H, Kolson D, NATHANSON N . An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992; 66(12):7517-21. PMC: 240461. DOI: 10.1128/JVI.66.12.7517-7521.1992. View

12.

Gringeri A, Musicco M, Hermans P, Bentwich Z, Cusini M, Bergamasco A . Active anti-interferon-alpha immunization: a European-Israeli, randomized, double-blind, placebo-controlled clinical trial in 242 HIV-1--infected patients (the EURIS study). J Acquir Immune Defic Syndr Hum Retrovirol. 1999; 20(4):358-70. DOI: 10.1097/00042560-199904010-00006. View

13.

Le Buanec H, Lachgar A, Bizzini B, Zagury J, Rappaport J, Santagostino E . A prophylactic and therapeutic AIDS vaccine containing as a component the innocuous Tat toxoid. Biomed Pharmacother. 1999; 52(10):431-5. DOI: 10.1016/s0753-3322(99)80020-1. View

14.

Gringeri A, Santagostino E, Muca-Perja M, Le Buanec H, Bizzini B, Lachgar A . Tat toxoid as a component of a preventive vaccine in seronegative subjects. J Acquir Immune Defic Syndr Hum Retrovirol. 1999; 20(4):371-5. DOI: 10.1097/00042560-199904010-00007. View

15.

Albini A, Ferrini S, Benelli R, Sforzini S, Giunciuglio D, Aluigi M . HIV-1 Tat protein mimicry of chemokines. Proc Natl Acad Sci U S A. 1998; 95(22):13153-8. PMC: 23742. DOI: 10.1073/pnas.95.22.13153. View

16.

Ensoli B, Barillari G, Salahuddin S, Gallo R, Wong-Staal F . Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature. 1990; 345(6270):84-6. DOI: 10.1038/345084a0. View

17.

Rasty S, Thatikunta P, Gordon J, Khalili K, Amini S, Glorioso J . Human immunodeficiency virus tat gene transfer to the murine central nervous system using a replication-defective herpes simplex virus vector stimulates transforming growth factor beta 1 gene expression. Proc Natl Acad Sci U S A. 1996; 93(12):6073-8. PMC: 39191. DOI: 10.1073/pnas.93.12.6073. View

18.

Frankel A, Pabo C . Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988; 55(6):1189-93. DOI: 10.1016/0092-8674(88)90263-2. View

19.

Westendorp M, Frank R, Ochsenbauer C, Stricker K, Dhein J, Walczak H . Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995; 375(6531):497-500. DOI: 10.1038/375497a0. View

20.

Dykhuizen M, Ceman J, Mitchen J, Zayas M, MacDougall A, Helgeland J . Importance of the CD3 marker for evaluating changes in rhesus macaque CD4/CD8 T-cell ratios. Cytometry. 2000; 40(1):69-75. DOI: 10.1002/(sici)1097-0320(20000501)40:1<69::aid-cyto9>3.0.co;2-7. View