Modulation of DNA Vaccine-Elicited CD8 super(+) T-Lymphocyte Epitope Immunodominance Hierarchies

• Published in: Journal of virology Vol. 80; no. 24; pp. 11991 - 11997
• Main Authors: Liu, Jinyan, Ewald, Bonnie A, Lynch, Diana M, Nanda, Anjali, Sumida, Shawn M, Barouch, Dan H
• Format: Journal Article
• Language: English
• Published: 01.12.2006
• Subjects: Human immunodeficiency virus 1; Simian immunodeficiency virus
• ISSN: 0022-538X; 1098-5514

Generating broad cellular immune responses against a diversity of viral epitopes is a major goal of current vaccine strategies for human immunodeficiency virus type 1 (HIV-1) and other pathogens. Virus-specific CD8 super(+) T-lymphocyte responses, however, are often highly focused on a very limited number of immunodominant epitopes. For an HIV-1 vaccine, the breadth of CD8 super(+) T-lymphocyte responses may prove to be critical as a result of the need to cover a wide diversity of viral isolates in the population and to limit viral escape from dominant epitope-specific T lymphocytes. Here we show that epitope modification strategies can alter CD8 super(+) T-lymphocyte epitope immunodominance hierarchies elicited by a DNA vaccine in mice. Mice immunized with a DNA vaccine expressing simian immunodeficiency virus Gag lacking the dominant D super(b)-restricted AL11 epitope generated a marked and durable augmentation of responses specific for the subdominant D super(b)-restricted KV9 epitope. Moreover, anatomic separation strategies and heterologous prime-boost regimens generated codominant responses against both epitopes. These data demonstrate that dominant epitopes can dramatically suppress the immunogenicity of subdominant epitopes in the context of gene-based vaccines and that epitope modification strategies can be utilized to enhance responses to subdominant epitopes.