HUMAN RHINOVIRUS TYPE-14 HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) V3 LOOP CHIMERAS FROM A COMBINATORIAL LIBRARY INDUCE POTENT NEUTRALIZING ANTIBODY-RESPONSES AGAINST HIV-1

In an effort to develop a useful AIDS vaccine or vaccine component, we have generated a combinatorial library of chimeric viruses in which t he sequence IGPGRAFYTTKN from the V3 loop of the MN strain of human im munodeficiency virus type 1 (HIV-1) is displayed in many conformations on the surface of human rhinovirus 14 (HRV14). The V3 loop sequence w as inserted into a naturally immunogenic site of the cold-causing HRV1 4, bridged by linkers consisting of zero to three randomized amino aci ds on each side. The library of chimeric viruses obtained was subjecte d to a variety of immunoselection schemes to isolate viruses that prov ided the most useful presentations of the V3 loop sequence for potenti al use in a vaccine against HIV. The utility of the presentations was assessed by measures of antigenicity and immunogenicity. Most of the i mmunoselected chimeras examined were potently neutralized by each of t he four different monoclonal anti-V3 loop antibodies tested. Seven of eight chimeric viruses were able to elicit neutralizing antibody respo nses in guinea pigs against the MN and ALA-1 strains of HIV-1. Three o f the chimeras elicited HIV neutralization titers that exceeded those of all but a small number of previously described HIV immunogens. Thes e results indicate that HRV14:HIV-1 chimeras may serve as useful immun ogens for stimulating immunity against HIV-1. This method can be used to flexibly reconstruct varied immunogens on the surface of a safe and immunogenic vaccine vehicle.