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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,
Kailash C.
Gupta,1,
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.

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

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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