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Journal of Virology, August 2005, p. 10200-10209, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10200-10209.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Replicating Rather than Nonreplicating Adenovirus-Human Immunodeficiency Virus Recombinant Vaccines Are Better at Eliciting Potent Cellular Immunity and Priming High-Titer Antibodies

Bo Peng,¹ Liqun Rejean Wang,^1, Victor Raúl Gómez-Román,^1, Alberta Davis-Warren,^1, David C. Montefiori,² V. S. Kalyanaraman,³ David Venzon,⁴ Jun Zhao,^1,|| Elaine Kan,⁵ Thomas J. Rowell,⁶ Krishna K. Murthy,⁷ Indresh Srivastava,⁵ Susan W. Barnett,⁵ and Marjorie Robert-Guroff^1*

Vaccine Branch,¹ Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland 20892,⁴ Department of Surgery, Laboratory for AIDS Vaccine Research & Development, Duke University Medical Center, Durham, North Carolina 27710,² Advanced BioScience Laboratories, Inc., Kensington, Maryland 20895,³ Chiron Corp., Emeryville, California 94608-2916,⁵ University of Louisiana at Lafayette, New Iberia Research Center, New Iberia, Louisiana 70560,⁶ Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227⁷

Received 23 March 2005/ Accepted 2 May 2005

A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1_MNenv/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIV_SF162 gp140V2. The immunogenicities of replicating and nonreplicating Ad/HIV-1_MNenv/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1_SF162 gp140V2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful.

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* Corresponding author. Mailing address: NIH, NCI, 41 Medlars Dr., Bldg. 41, Rm. D804; Bethesda, MD 20892-5065. Phone: (301) 496-2114. Fax: (301) 402-0055. E-mail:guroffm{at}mail.nih.gov.

Present address: University of Gainesville, Gainesville, FL 32606.

Present address: Chiron Corp., Emeryville, CA 94608-2916.

Present address: National Center for Research Resources, Office of Science Policy, Bethesda, MD 20892.

^|| Present address: Emory University, Atlanta, GA 30329.

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Journal of Virology, August 2005, p. 10200-10209, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10200-10209.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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