CHIMERAS FROM A HUMAN RHINOVIRUS 14-HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) V3 LOOP SEROPREVALENCE LIBRARY INDUCE NEUTRALIZING RESPONSES AGAINST HIV-1
Da. Resnick et al., CHIMERAS FROM A HUMAN RHINOVIRUS 14-HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) V3 LOOP SEROPREVALENCE LIBRARY INDUCE NEUTRALIZING RESPONSES AGAINST HIV-1, Journal of virology, 69(4), 1995, pp. 2406-2411
A chimeric virus library was designed whereby sequences corresponding
to the V3 loop of human immunodeficiency virus type 1 (HIV-1) were pre
sented on the surface of human rhinovirus 14. The V3 loop sequences co
nsisted of a relatively conserved segment of seven amino acids and fiv
e adjacent residues that were allowed to vary in proportion to their s
eroprevalence among HIV-1 isolates of North America and Europe. A tech
nique called random systematic mutagenesis was used to incorporate the
composite V3 loop sequences Banked by zero to two randomized amino ac
ids. This library could contain 2.7 x 10(8) members having diverse seq
uences and conformations. Immunoselection of a portion of this library
by using two neutralizing V3 loop directed monoclonal antibodies foll
owed by selection for desirable growth and purification characteristic
s yielded a set of chimeric rhinoviruses, five of which are described.
The inserted sequences in the five chimeras do not match those of any
known isolate of HIV-1. Nonetheless, all five chimeras were neutraliz
ed by antibodies directed against different strains of HIV-1 and were
able to elicit the production of antibodies that bind V3 loop peptides
from diverse HIV-1 isolates. Moreover, antisera derived from four of
the five chimeras were capable of neutralizing one or more strains of
HIV-1 in cell culture. This study demonstrates that random systematic
mutagenesis in conjunction with antibody screening is a powerful and e
fficient means to obtain antigenic chimeras with relevant immunogenic
properties.