Protective immunity to SIV challenge elicited by vaccination of macaques with multigenic DNA vaccines producing virus-like particles

Sally P. Mossman, Christopher C. Pierce, Andrew J. Watson, Michael N. Robertson, David C. Montefiori, Larene Kuller, Barbra A. Richardson, Jeffrey D. Bradshaw, Robert J. Munn, Shiu Lok Hu, Philip D. Greenberg, Raoul E. Benveniste, Nancy Haigwood

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We utilized SIVmne infection of Macaca fascicularis to assess the efficacy of DNA vaccination alone, and as a priming agent in combination with subunit protein boosts. All SIVmne 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 μg recombinant Env gp160 and 250 μg 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 SIVmne. 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.

Original languageEnglish (US)
Pages (from-to)425-434
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume20
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

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DNA Vaccines
Macaca
Virion
Immunity
Vaccination
Vaccines
DNA
Protein Subunits
CD4 Lymphocyte Count
Plasmids
Maintenance
T-Lymphocytes
Macaca fascicularis
Viremia
Regulator Genes
Humoral Immunity
Helper-Inducer T-Lymphocytes
Neutralizing Antibodies
Cytomegalovirus
Cellular Immunity

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Protective immunity to SIV challenge elicited by vaccination of macaques with multigenic DNA vaccines producing virus-like particles. / Mossman, Sally P.; Pierce, Christopher C.; Watson, Andrew J.; Robertson, Michael N.; Montefiori, David C.; Kuller, Larene; Richardson, Barbra A.; Bradshaw, Jeffrey D.; Munn, Robert J.; Hu, Shiu Lok; Greenberg, Philip D.; Benveniste, Raoul E.; Haigwood, Nancy.

In: AIDS Research and Human Retroviruses, Vol. 20, No. 4, 04.2004, p. 425-434.

Research output: Contribution to journalArticle

Mossman, SP, Pierce, CC, Watson, AJ, Robertson, MN, Montefiori, DC, Kuller, L, Richardson, BA, Bradshaw, JD, Munn, RJ, Hu, SL, Greenberg, PD, Benveniste, RE & Haigwood, N 2004, 'Protective immunity to SIV challenge elicited by vaccination of macaques with multigenic DNA vaccines producing virus-like particles', AIDS Research and Human Retroviruses, vol. 20, no. 4, pp. 425-434. https://doi.org/10.1089/088922204323048177
Mossman, Sally P. ; Pierce, Christopher C. ; Watson, Andrew J. ; Robertson, Michael N. ; Montefiori, David C. ; Kuller, Larene ; Richardson, Barbra A. ; Bradshaw, Jeffrey D. ; Munn, Robert J. ; Hu, Shiu Lok ; Greenberg, Philip D. ; Benveniste, Raoul E. ; Haigwood, Nancy. / Protective immunity to SIV challenge elicited by vaccination of macaques with multigenic DNA vaccines producing virus-like particles. In: AIDS Research and Human Retroviruses. 2004 ; Vol. 20, No. 4. pp. 425-434.
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