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Journal of Virology, April 2006, p. 3732-3742, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3732-3742.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Systemic Immunization with an ALVAC-HIV-1/Protein Boost Vaccine Strategy Protects Rhesus Macaques from CD4+ T-Cell Loss and Reduces both Systemic and Mucosal Simian-Human Immunodeficiency Virus SHIVKU2 RNA Levels

Ranajit Pal,1 David Venzon,2 Sampa Santra,3 Vaniambadi S. Kalyanaraman,1 David C. Montefiori,4 Lindsey Hocker,1 Lauren Hudacik,1 Nicolas Rose,1 Janos Nacsa,5 Yvette Edghill-Smith,5,6 Marcin Moniuszko,5,7 Zdenek Hel,5,8 Igor M. Belyakov,9 Jay A. Berzofsky,9 Robyn Washington Parks,5 Phillip D. Markham,1 Norman L. Letvin,3 Jim Tartaglia,10 and Genoveffa Franchini5*

Advanced BioScience Laboratories, Inc., 5510 Nicholson Lane, Kensington, Maryland 20895,1 Biostatistics and Data Management Section, National Cancer Institute, 6116 Executive Boulevard, MSC 8325, Suite 702, Bethesda, Maryland 20892,2 Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P. O. Box 15732, Boston, Massachusetts 02215,3 Department of Surgery, Center for AIDS Research, Duke University Medical Center, Box 2926, Durham, North Carolina 27710,4 Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, 41/D804, Bethesda, Maryland 20892,5 Southern Research Institute, 431 Aviation Way, Frederick, Maryland 21701,6 Department of Allergology and Internal Diseases, Medical University of Bialystok, ul. Sklodowskiej 24 A, 15-276, Bialystok, Poland,7 Department of Pathology, Center for AIDS Research, University of Alabama at Birmingham, 619 19th Street South, Room SW-W286, Birmingham, Alabama 35249,8 Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, National Cancer Institute, 10/6B12, Bethesda, Maryland 20892,9 Sanofi Pasteur, 1755 Steeles Avenue West, Toronto, M2R 3T4 Ontario, Canada,10

Received 2 November 2005/ Accepted 20 December 2005

Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines expressing Gag, Pol, and gp120 (vCP250) or Gag, Pol, and gp160 (vCP1420) in a prime-boost protocol with their homologous vaccine native Env proteins. The relative efficacy was measured against a high-dose mucosal exposure to the pathogenic neutralization-resistant variant SHIVKU2 (simian-human immunodeficiency virus). Systemic immunization with both vaccine regimens decreased viral load levels not only in blood but unexpectedly also in mucosal sites and protected macaques from peripheral CD4+ T-cell loss. This protective effect was stronger when the gp120 antigen was included in the vaccine. Inclusion of recombinant Tat protein in the boosting phase along with the Env protein did not contribute further to the preservation of CD4+ T cells. Thus, systemic immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune responses able to contain virus replication also at mucosal sites in macaques.

* Corresponding author. Mailing address: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, 41/D804, Bethesda, MD 20892. Phone: (301) 496-2386. Fax: (301) 402-0055. E-mail: franchig{at}mail.nih.gov.

Journal of Virology, April 2006, p. 3732-3742, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3732-3742.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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