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310 Combinatorial Libraries of Chimeric Human Rhinoviruses Displaying HIV-1 Immunogens in Diverse Conformations
G. Arnold*1,2, E. Bayman1,2, C. Tu1,3, X. Ma1,2, P. Velasco1,4, S. Geisler1,2, D. Montefiori5, and E. Arnold1
1Ctr. for Advanced Biotechnology and Med., New Brunswick, NJ, USA; 2Rutgers Univ., New Brunswick, NJ, USA; 3Changchun Univ. of Agricultural and Animal Sci., China; 4Univ. of Med. and Dentistry of New Jersey, Piscataway, USA; and 5Duke Univ. Med. Ctr., Durham, NC, USA
Background: Our goal is to generate and identify presentations of HIV-1 immunogens on the surface of the cold-causing human rhinovirus (HRV) that will be capable of eliciting neutralizing antibodies against diverse isolates of HIV-1. HRV is known to stimulate potent humoral immune responses, including mucosal responses. The 2 HIV-1 immunogens that we have targeted are (1) the ELDKWA immunogen (corresponding to the conserved gp41 ectodomain residues 662(667) and (2) the V3 loop of gp120.
Methods: We have generated combinatorial libraries of chimeric HRV:HIV viruses in which the HIV-1 sequence is inserted into a surface-exposed immunogenic loop of HRV via linkers of variable length and sequence and, in some cases, flanked by a potential disulfide bond. The V3 loop sequences consist of composites of known HIV sequences in hopes of eliciting cross-reactive immune responses. Using immunoselection, we have sequentially enriched for chimeric viruses that are well recognized by anti-HIV-1 antibodies (the human mAb 447, HIVIG, and/or human mAb 2F5). We have characterized immunoselected viruses for their ability to bind to and be neutralized by HIV-1 antibodies using competitive ELISA and MTT assays.
Results: Chimeric HRV:HIV viruses have been identified that elicit antibody responses in guinea pigs that in some cases demonstrate HIV-1-specific neutralizing activity in vitro. Additional studies are underway to optimize
these immunogens for cross-reactive neutralizing antibody induction against a broad spectrum of HIV-1 variants.
Conclusions: Chimeric HRV:HIV viruses able to elicit potent and cross-reactive antibodies against diverse HIV-1 isolates could be valuable AIDS vaccines or vaccine components.
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