1. Protective immunity to SIV challenge elicited by vaccination of macaques with multigenic DNA vaccines producing virus-like particles.
- Author
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Mossman SP, Pierce CC, Watson AJ, Robertson MN, Montefiori DC, Kuller L, Richardson BA, Bradshaw JD, Munn RJ, Hu SL, Greenberg PD, Benveniste RE, and Haigwood NL
- Subjects
- Animals, Antibodies, Viral blood, Antigens, Viral immunology, CD4 Lymphocyte Count, Fusion Proteins, gag-pol genetics, Fusion Proteins, gag-pol immunology, Gene Products, env immunology, HIV Envelope Protein gp160 genetics, HIV Envelope Protein gp160 immunology, Immunity, Cellular, Macaca fascicularis, Neutralization Tests, Plasmids, Proviruses genetics, Proviruses isolation & purification, RNA, Viral blood, SAIDS Vaccines administration & dosage, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Acquired Immunodeficiency Syndrome virology, Vaccines, DNA administration & dosage, Vaccines, Subunit administration & dosage, Vaccines, Subunit immunology, Viral Load, SAIDS Vaccines immunology, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus immunology, Vaccines, DNA immunology
- Abstract
We utilized SIV(mne) infection of Macaca fascicularis to assess the efficacy of DNA vaccination alone, and as a priming agent in combination with subunit protein boosts. All SIV(mne) structural and regulatory genes were expressed using the human cytomegalovirus Immediate Early-1 promoter in plasmids that directed the formation of virus-like particles in vitro. Macaques (n = 4) were immunized intradermally and intramuscularly four times over 36 weeks with 3 mg plasmid DNA. A second group (n = 4) received two DNA priming inoculations followed by two intramuscular boosts consisting of 250 microg recombinant Env gp160 and 250 microg recombinant Gag-Pol particles in MF-59 adjuvant. These regimens elicited modest cellular immunity prior to challenge. Humoral immune responses to Env gp160 were elicited and sustained by both vaccine protocols, and as expected antibody titers were higher in the protein subunit-boosted animals. Neutralizing antibodies prior to challenge were measurable in two of four subunit-boosted macaques. The two vaccine regimens elicited comparable helper T cell responses at the time of challenge. Vaccinees and mock-immunized controls (n = 4) were challenged intrarectally at week 38 with uncloned SIV(mne). Following challenge all macaques became infected, but both vaccine regimens resulted in reduced peak virus loads (p = 0.07) and significantly improved maintenance of peripheral CD4(+) T cell counts postchallenge (p = 0.007, DNA alone and p = 0.01, all vaccinees). There was no significant difference between the two vaccine groups in levels of plasma viremia or maintenance of CD4(+) T cell counts postchallenge.
- Published
- 2004
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