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Title
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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.
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Authors
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A.D.Smith,
S.C.Geisler,
A.A.Chen,
D.A.Resnick,
B.M.Roy,
P.J.Lewi,
E.Arnold,
G.F.Arnold.
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Ref.
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J Virol, 1998,
72,
651-659.
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PubMed id
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Abstract
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In an effort to develop a useful AIDS vaccine or vaccine component, we have
generated a combinatorial library of chimeric viruses in which the sequence
IGPGRAFYTTKN from the V3 loop of the MN strain of human immunodeficiency virus
type 1 (HIV-1) is displayed in many conformations on the surface of human
rhinovirus 14 (HRV14). The V3 loop sequence was inserted into a naturally
immunogenic site of the cold-causing HRV14, bridged by linkers consisting of
zero to three randomized amino acids on each side. The library of chimeric
viruses obtained was subjected to a variety of immunoselection schemes to
isolate viruses that provided the most useful presentations of the V3 loop
sequence for potential use in a vaccine against HIV. The utility of the
presentations was assessed by measures of antigenicity and immunogenicity. Most
of the immunoselected chimeras examined were potently neutralized by each of the
four different monoclonal anti-V3 loop antibodies tested. Seven of eight
chimeric viruses were able to elicit neutralizing antibody responses in guinea
pigs against the MN and ALA-1 strains of HIV-1. Three of the chimeras elicited
HIV neutralization titers that exceeded those of all but a small number of
previously described HIV immunogens. These results indicate that HRV14:HIV-1
chimeras may serve as useful immunogens 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.
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