Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric Env protein boost in the SHIV rhesus macaque model.
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.
Earl
Patricia L
PL
Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. pearl@atlas.niaid.nih.gov
Wyatt
Linda S
LS
Montefiori
David C
DC
Bilska
Miroslawa
M
Woodward
Ruth
R
Markham
Phillip D
PD
Malley
James D
JD
Vogel
Thorsten U
TU
Allen
Todd M
TM
Watkins
David I
DI
Miller
Nancy
N
Moss
Bernard
B
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D008253:Macaca mulatta; D009842:Oligopeptides / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D015483:HIV Antibodies; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1