Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

Author:

Casimiro Danilo R.1,Tang Aimin1,Chen Ling1,Fu Tong-Ming1,Evans Robert K.2,Davies Mary-Ellen1,Freed Daniel C.1,Hurni William3,Aste-Amezaga Jose M.3,Guan Liming1,Long Romnie1,Huang Lingyi1,Harris Virginia1,Nawrocki Denise K.1,Mach Henryk2,Troutman Robert D.2,Isopi Lynne A.2,Murthy Krishna K.4,Rice Karen4,Wilson Keith A.1,Volkin David B.1,Emini Emilio A.1,Shiver John W.1

Affiliation:

1. Departments of Viral Vaccine Research

2. Vaccine Pharmaceutical Research and Development

3. Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486

4. Department of Virology and Immunology, Southwest Foundation for Medical Research, San Antonio, Texas 78245

Abstract

ABSTRACT The cellular immunogenicity of formulated plasmid DNA and replication-defective human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized human immunodeficiency virus type 1 gag gene was examined in baboons. The Ad5 vaccine was capable of inducing consistently strong, long-lived CD8 + -biased T-cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune responses were weaker than those elicited by the Ad5 vaccine and highly variable; formulation with chemical adjuvants led to moderate increases in the levels of Gag-specific T cells. Increasing the DNA-primed responses with booster doses of either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in the relative levels of cytotoxic and helper responses. The implications of these results are discussed.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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