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Journal of Virology, November 1998, p. 9069-9078, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Oral Immunization of Macaques with Attenuated Vaccine Virus Induces Protection against Vaginally Transmitted AIDS

Sanjay V. Joag,1 Zhen Qian Liu,1 Edward B. Stephens,1 Marilyn S. Smith,1 Anil Kumar,1 Zhuang Li,1 Chunyang Wang,1 Darlene Sheffer,1 Fenglan Jia,1 Larry Foresman,1 Istvan Adany,1 Jeff Lifson,2 Harold M. McClure,3 and Opendra Narayan1,*

Marion Merrell Dow Laboratory of Viral Pathogenesis and Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, Kansas 661601; NCI-Frederick Cancer Research, Frederick, Maryland 217022; and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 303223

Received 5 June 1998/Accepted 24 July 1998

The chimeric simian-human immunodeficiency virus SHIVKU-1, bearing the envelope of human immunodeficiency virus type 1 (HIV-1), causes fulminant infection with subtotal loss of CD4+ T cells followed by development of AIDS in intravaginally inoculated macaques and thus provides a highly relevant model of sexually transmitted disease caused by HIV-1 in human beings. Previous studies using this SHIV model had shown that the vpu and nef genes were important in pathogenesis of the infection, and so we deleted portions of these genes to create two vaccines, Delta vpuDelta nefSHIV-4 (vaccine 1) and Delta vpuSHIVPPc (vaccine 2). Six adult macaques were immunized subcutaneously with vaccine 1, and six were immunized orally with vaccine 2. Both viruses caused infection in all inoculated animals, but whereas vaccine 1 virus caused only a nonproductive type of infection, vaccine 2 virus replicated productively but transiently for a 6- to 10-week period. Both groups were challenged 6 to 7 months later with pathogenic SHIVKU-1 by the intravaginal route. All four unvaccinated controls developed low CD4+ T-cell counts (<200/µl) and AIDS. The 12 vaccinated animals all became infected with SHIVKU-1, and two in group 1 developed a persistent productive infection followed by development of AIDS in one. The other 10 have maintained almost complete control over virus replication even though spliced viral RNA was detected in lymph nodes. This suppression of virus replication correlated with robust antiviral cell-mediated immune responses. This is the first demonstration of protection against virulent SHIV administered by the intravaginal route. This study supports the concept that sexually transmitted HIV disease can be prevented by parenteral or oral immunization.

* Corresponding author. Mailing address: Marion Merrell Dow Laboratory of Viral Pathogenesis, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7424. Phone: (913) 588-5575. Fax: (913) 588-5599. E-mail: bnarayan{at}kumc.edu.

Journal of Virology, November 1998, p. 9069-9078, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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