Weaver EA, Lu Z, Li Y, Liao HX, Ma B, Alam MS, Scearce RM, Sutherland L, Decker JM, Hartman Z, Amalfitano A, Shaw GM, Korber BT, Hahn BH, Montefiori DC, Haynes BF, Gao F; Conference on Retroviruses and Opportunistic Infections (11th : 2004 : San Francisco, Calif.).
Program Abstr Conf Retrovir Oppor Infect 11th 2004 San Franc Calif. 2004 Feb 8-11; 11: abstract no. 164.
Duke Univ. Med. Ctr., Durham, NC, USA
BACKGROUND: The high level of genetic variation in HIV-1 represents a major obstacle for AIDS vaccine development. To decrease the genetic distance between candidate immunogens and field virus strains, we have generated a group M consensus env gene (CON6) that is equidistant from any subtype or recombinant viruses. This novel artificial env gene is biologically functional, possesses linear, conformational and glycan-dependent epitopes, and exhibits broad cross-recognition by different subtype sera as compared to subtype-specific env antigens.METHODS: To compare the immune responses induced by CON6 Env immunogens (gp120 and gp140CF) to those induced by subtype B and C gp120 immunogens derived from JRFL and 96ZM651, respectively, 3 strains of mice (BALB/c, C57BL/6, and C3H) were primed with either DNA or recombinant adenoviruses (rAd) and boosted with recombinant vaccinia viruses (rVV). The splenocytes were harvested, stimulated with 3 Env overlapping peptide pools (CON6, MN_B, and Chn19_C) and the T-cell immune responses were measured using the ELISpot assay. To assess neutralizing antibody induction, guinea pigs were primed with DNA and boosted with rVV, protein, or rAd. Guinea pigs were also immunized with CON6 proteins only. Neutralization activities were measured using a luciferase-based assay with a TCLA strain (MN) and primary HIV-1 isolates of multiple subtypes.RESULTS: Cross-subtype T-cell immune responses induced by CON6 immunogens were detected after stimulation with peptides from all 3 peptide pools in all 3 strains of mice. T-cell immune responses were detected for the JRFL immunogen only when stimulated with clade B peptide pools; whereas, T-cell immune responses induced by the 96ZM651 immunogen were detected after stimulation with subtype C and CON6 peptide pools in BALB/c mice. The antibodies induced by CON6 immunogens in guinea pigs neutralized a TCLA strain (MN) at high titers and demonstrated detectable neutralizing activity against select primary HIV isolates from subtypes A, B, C, D, and CRF01_AE.CONCLUSIONS: The group M artificial consensus Env gp120 and gp140CF proteins were antigenic and immunogenic, and could induce cross-subtype T- and B-cell immune responses, including neutralizing antibodies.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Animals
- B-Lymphocytes
- Epitopes
- Gene Products, env
- Genes, env
- HIV
- HIV Antibodies
- HIV Antigens
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seropositivity
- HIV-1
- Mice
- T-Lymphocytes
- Vaccinia virus
- genetics
- immunology
Other ID:
UI: 102270871
From Meeting Abstracts