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J Virol, January 1998, p. 651-659, Vol. 72, No. 1
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Allen D. Smith,¹ Sheila C. Geisler,¹ Anne A. Chen,^1, Dawn A. Resnick,^1, Birgit M. Roy,^1,§ Paul J. Lewi,² Edward Arnold,^1,* and Gail Ferstandig Arnold^1,*

Center for Advanced Biotechnology and Medicine and Department of Chemistry, Rutgers University, Piscataway, New Jersey 08854,¹ and Center for Molecular Design, Janssen Research Foundation, Vosselaar, Belgium²

Received 17 June 1997/Accepted 26 September 1997

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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^* Corresponding author. Mailing address: CABM and Rutgers University, 679 Hoes La., Piscataway, NJ 08854-5638. Phone: (732) 235-4343 (G. F. Arnold) and (732) 235-5323 (E. Arnold). Fax: (732) 235-5788. E-mail: gfarnold{at}cabm.rutgers.edu (G. F. Arnold) and arnold{at}cabm.rutgers.edu (E. Arnold).

Present address: Albert Einstein College of Medicine, Bronx, New York, NY 10461.

Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

^§ Present address: Wyeth-Ayerst Research, Princeton, NJ 08540.

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