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Journal of Virology, October 2003, p. 10348-10356, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10348-10356.2003

Cellular Immunity Elicited by Human Immunodeficiency Virus Type 1/ Simian Immunodeficiency Virus DNA Vaccination Does Not Augment the Sterile Protection Afforded by Passive Infusion of Neutralizing Antibodies

John R. Mascola,1* Mark G. Lewis,2 Thomas C. VanCott,3 Gabriela Stiegler,4 Hermann Katinger,4 Michael Seaman,5 Kristin Beaudry,5 Dan H. Barouch,5 Birgit Korioth-Schmitz,5 Georgia Krivulka,5 Anna Sambor,1 Brent Welcher,1 Daniel C. Douek,1 David C. Montefiori,6 John W. Shiver,7 Pascal Poignard,8 Dennis R. Burton,8 and Norman L. Letvin5

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Southern Research Institute, Frederick, Maryland 21701,2 U.S. Military HIV Research Program, Henry Jackson Foundation, Rockville, Maryland 20850,3 Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Vienna, Austria,4 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,5 Duke University Medical Center, Durham, North Carolina 27710,6 Merck Research Laboratories, West Point, Pennsylvania 19486,7 Scripps Research Institute, La Jolla, California 920938

Received 17 April 2003/ Accepted 28 June 2003

High levels of infused anti-human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibodies (MAbs) can completely protect macaque monkeys against mucosal chimeric simian-human immunodeficiency virus (SHIV) infection. Antibody levels below the protective threshold do not prevent infection but can substantially reduce plasma viremia. To assess if HIV-1/SIV-specific cellular immunity could combine with antibodies to produce sterile protection, we studied the effect of a suboptimal infusion of anti-HIV-1 neutralizing antibodies in macaques with active cellular immunity induced by interleukin-2 (IL-2)-adjuvanted DNA immunization. Twenty female macaques were divided into four groups: (i) DNA immunization plus irrelevant antibody, (ii) DNA immunization plus infusion of neutralizing MAbs 2F5 and 2G12, (iii) sham DNA plus 2F5 and 2G12, and (iv) sham DNA plus irrelevant antibody. DNA-immunized monkeys developed CD4 and CD8 T-cell responses as measured by epitope-specific tetramer staining and by pooled peptide ELISPOT assays for gamma interferon-secreting cells. After vaginal challenge, DNA-immunized animals that received irrelevant antibody became SHIV infected but displayed lower plasma viremia than control animals. Complete protection against SHIV challenge occurred in three animals that received sham DNA plus MAbs 2F5 and 2G12 and in two animals that received the DNA vaccine plus MAbs 2F5 and 2G12. Thus, although DNA immunization produced robust HIV-specific T-cell responses, we were unable to demonstrate that these responses contributed to the sterile protection mediated by passive infusion of neutralizing antibodies. These data suggest that although effector T cells can limit viral replication, they are not able to assist humoral immunity to prevent the establishment of initial infection.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID, NIH, 40 Convent Dr., Bethesda, MD 20892. Phone: (301) 594-8487. Fax: (301) 480-2788. E-mail: jmascola{at}nih.gov.

Journal of Virology, October 2003, p. 10348-10356, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10348-10356.2003




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