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Journal of Virology, March 2001, p. 2224-2234, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2224-2234.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Polyvalent Envelope Glycoprotein Vaccine Elicits a Broader Neutralizing Antibody Response but Is Unable To Provide Sterilizing Protection against Heterologous Simian/Human Immunodeficiency Virus Infection in Pigtailed Macaques

Michael W. Cho,1,* Young B. Kim,1 Myung K. Lee,1,dagger Kailash C. Gupta,1,Dagger Will Ross,1 Ron Plishka,1 Alicia Buckler-White,1 Tatsuhiko Igarashi,1 Ted Theodore,1 Russ Byrum,2 Chris Kemp,3 David C. Montefiori,4 and Malcolm A. Martin1

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-04601; Bioqual, Rockville, Maryland 208502; Kemp Biotechnologies, Inc., Frederick, Maryland 217043; and Department of Surgery, Duke University Medical Center, Durham, North Carolina 277104

Received 27 September 2000/Accepted 7 December 2000

The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus type 1 (HIV-1) isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosylation, and marked genetic variability. Most previously evaluated vaccine candidates have utilized envelope glycoprotein from a single virus isolate. Here we compare the breadth of NAb and protective immune response following vaccination of pigtailed macaques with envelope protein(s) derived from either single or multiple viral isolates. Animals were challenged with Simian/human immunodeficiency virus strain DH12 (SHIVDH12) following priming with recombinant vaccinia virus(es) expressing gp160(s) and boosting with gp120 protein(s) from (i) LAI, RF, 89.6, AD8, and Bal (Polyvalent); (ii) LAI, RF, 89.6, AD8, Bal, and DH12 (Polyvalent-DH12); (iii) 89.6 (Monovalent-89.6); and (iv) DH12 (Monovalent-DH12). Animals in the two polyvalent vaccine groups developed NAbs against more HIV-1 isolates than those in the two monovalent vaccine groups (P = 0.0054). However, the increased breadth of response was directed almost entirely against the vaccine strains. Resistance to SHIVDH12 strongly correlated with the level of NAbs directed against the virus on the day of challenge (P = 0.0008). Accordingly, the animals in the Monovalent-DH12 and Polyvalent-DH12 vaccine groups were more resistant to the SHIVDH12 challenge than the macaques immunized with preparations lacking a DH12 component (viz. Polyvalent and Monovalent-89.6) (P = 0.039). Despite the absence of any detectable NAb, animals in the Polyvalent vaccine group, but not those immunized with Monovalent-89.6, exhibited markedly lower levels of plasma virus than those in the control group, suggesting a superior cell-mediated immune response induced by the polyvalent vaccine.


* Corresponding author. Mailing address: Laboratory of Molecular Microbiology, NIH, NIAID, 9000 Rockville Pike, Bldg. 4, Rm. 339, Bethesda, MD 20892-0460. Phone: (301) 496-0576. Fax: (301) 402-0226. E-mail: mcho{at}nih.gov.

dagger Present address: Protein Engineering Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon 305-600, Republic of Korea.

Dagger Present address: Rush Presbyterian-St. Luke's Medical Center, Dept. of Immunology/Microbiology, Chicago, IL 60612-3833.


Journal of Virology, March 2001, p. 2224-2234, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2224-2234.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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