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Journal of Virology, March 2004, p. 2212-2221, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2212-2221.2004

Protection against Mucosal Simian Immunodeficiency Virus SIVmac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

L. Jean Patterson,1 Nina Malkevitch,1 David Venzon,2 Joel Pinczewski,1 Victor Raúl Gómez-Román,1 Liqun Wang,1 V. S. Kalyanaraman,3 Phillip D. Markham,3 Frank A. Robey,4 and Marjorie Robert-Guroff1*

Basic Research Laboratory,1 Biostatistics and Data Management Section, National Cancer Institute,2 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892,4 Advanced Bioscience Laboratories, Inc., Kensington, Maryland 208953

Received 14 July 2003/ Accepted 12 November 2003

Whereas several recent AIDS vaccine strategies have protected rhesus macaques against a pathogenic simian/human immunodeficiency virus (SHIV)89.6P challenge, similar approaches have provided only modest, transient reductions in viral burden after challenge with virulent, pathogenic SIV, which is more representative of HIV infection of people. We show here that priming with replicating adenovirus recombinants encoding SIV env/rev, gag, and/or nef genes, followed by boosting with SIV gp120 or an SIV polypeptide mimicking the CD4 binding region of the envelope, protects rhesus macaques from intrarectal infection with the highly pathogenic SIVmac251. Using trend analysis, significant reductions in acute-phase and set point viremia were correlated with anti-gp120 antibody and cellular immune responses, respectively. Within immunization groups exhibiting significant protection, a subset (39%) of macaques have exhibited either no viremia, cleared viremia, or controlled viremia at the threshold of detection, now more than 40 weeks postchallenge. This combination prime-boost strategy, utilizing replication competent adenovirus, is a promising alternative for HIV vaccine development.

* Corresponding author. Mailing address: NIH, NCI, 41 Medlars Dr., MSC5065, Bldg. 41, Rm. D804, Bethesda, MD 20892-5065. Phone: (301) 496-2114. Fax: (301) 496-8394. E-mail: guroffm{at}mail.nih.gov.

Journal of Virology, March 2004, p. 2212-2221, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2212-2221.2004




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