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Comparison of Vaccine Strategies Using Recombinant env–gag–pol MVA with or without an Oligomeric Env Protein Boost in the SHIV Rhesus Macaque Model

2002; Elsevier BV; Volume: 294; Issue: 2 Linguagem: Inglês

10.1006/viro.2001.1345

1096-0341

Patricia L. Earl, Linda S. Wyatt, David C. Montefiori, Miroslawa Bilska, Ruth Woodward, Phillip D. Markham, James D. Malley, Thorsten U. Vogel, Todd M. Allen, David I. Watkins, N. R. Miller, Bernard Moss,

Virus-based gene therapy research

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.