Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric Env protein boost in the SHIV rhesus macaque model.

Published

Journal Article

Rhesus macaques were immunized with a replication-deficient vaccinia virus (MVA) expressing human immunodeficiency virus type 1 89.6 envelope (env) and SIV gagpol (MVA/SHIV89.6) with or without a protein boost consisting of soluble 89.6 env (gp140). Immunization with MVA/SHIV89.6 alone elicited binding antibodies in all animals and neutralizing antibodies in 5 of 15 animals. Both types of antibodies were enhanced by protein boosting. In addition, CD8 cells exhibiting CM9 tetramer binding were detected in the subset of animals that were Mamu-A*01 positive. Animals were challenged intravenously with either SHIV-89.6 (Study 1) or the more pathogenic derivative SHIV-89.6P (Study 2). In Study 1, all control and vaccinated animals except one became infected. However, the levels of viremia were as follows: controls > rMVA alone > rMVA + protein. The differences were statistically significant between immunized and control groups but not between the two immunized groups. In Study 2, all animals became infected; however, the vaccinated group exhibited a 5-fold reduction in peak viremia and a 10-fold reduction in the postacute phase viremia in comparison to the controls. All of the controls required euthanasia by 10 months after challenge. A relationship between vaccine-induced antibody titers and reduction in virus burden was observed in both studies. Thus, immunization with MVA/SHIV89.6 alone or with a protein boost stimulated both arms of the immune system and resulted in significant control of viremia and delayed progression to disease after challenge with SHIV-89.6P.

Full Text

Duke Authors

Cited Authors

  • Earl, PL; Wyatt, LS; Montefiori, DC; Bilska, M; Woodward, R; Markham, PD; Malley, JD; Vogel, TU; Allen, TM; Watkins, DI; Miller, N; Moss, B

Published Date

  • March 15, 2002

Published In

Volume / Issue

  • 294 / 2

Start / End Page

  • 270 - 281

PubMed ID

  • 12009868

Pubmed Central ID

  • 12009868

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1006/viro.2001.1345

Language

  • eng

Conference Location

  • United States