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Journal of Virology, November 1999, p. 9485-9495, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mucosal Immunization of Cynomolgus Macaques with Two Serotypes of Live Poliovirus Vectors Expressing Simian Immunodeficiency Virus Antigens: Stimulation of Humoral, Mucosal, and Cellular Immunitydagger

Shane Crotty,1 Barbara L. Lohman,2 Fabien X.-S. Lü,2 ShenBei Tang,1 Christopher J. Miller,2,3 and Raul Andino1,*

Department of Microbiology and Immunology, University of California, San Francisco, California 94143,1 and California Regional Primate Research Center, Department of Pathology, School of Medicine,2 and Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, and Center for Comparative Medicine,3 University of California, Davis, California 95616

Received 15 April 1999/Accepted 9 August 1999

Poliovirus live virus vectors are a candidate recombinant vaccine system. Previous studies using this system showed that a live poliovirus vector expressing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses involving a hybrid-PCR approach. We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17gag and gp41env. All macaques generated a mucosal anti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the four macaques generated mucosal antibody responses detectable in vaginal lavages. Strong serum IgG responses lasting for at least 1 year were detected in two of the four monkeys. SIV-specific T-cell lymphoproliferative responses were detected in three of the four monkeys. SIV-specific cytotoxic T lymphocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any naturally infectable primate, including humans. These findings support the concept that a live poliovirus vector is a potentially useful delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of California, Box 0414, San Francisco, CA 94143. Phone: (415) 502-7196. Fax: (415) 476-0939. E-mail: pandino{at}itsa.ucsf.edu.

dagger Dedicated to the memory of Rob Sadler (1963-1999).

Journal of Virology, November 1999, p. 9485-9495, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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