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Journal of Virology, January 2004, p. 1020-1025, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.1020-1025.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mucosal and Systemic Immune Responses to a Human Immunodeficiency Virus Type 1 Epitope Induced upon Vaginal Infection with a Recombinant Influenza A Virus

Bruno Garulli,1,{dagger} Yoshihiro Kawaoka,2,3,4 and Maria R. Castrucci1*

Laboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy,1 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706,2 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,3 CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan4

Received 14 July 2003/ Accepted 3 October 2003

The humoral and cellular immune responses in the genital mucosa likely play an important role in the prevention of sexually transmitted infections, including infection with human immunodeficiency virus type 1 (HIV-1). Here we show that vaginal infection of progesterone-treated BALB/c mice with a recombinant influenza virus bearing the immunodominant P18IIIB cytotoxic T-lymphocyte (CTL) epitope of the gp160 envelope protein from an HIV-1 IIIB isolate (P18IIIB; RIQRGPGRAFVTIGK) can induce a specific immune response in regional mucosal lymph nodes, as well as in a systemic site (the spleen). A single inoculation of mice with the recombinant influenza virus induced long-lasting (at least 5 months) antigen-specific CTL memory detectable as a rapid recall of effector CTLs upon vaginal infection with recombinant vaccinia virus expressing HIV-1 IIIB envelope gene products. Long-term antigen-specific CTL memory was also induced and maintained in distant mucosal tissues when mice were intranasally immunized with the recombinant influenza virus. These results indicate that mucosal immunization and, in particular, local vaginal immunization with recombinant influenza virus can provide strong, durable immune responses in the female genital tract of mice.

* Corresponding author. Mailing address: Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39-06-49903259. Fax: 39-06-49902082. E-mail: maria.castrucci{at}iss.it.

{dagger} Present address: Department of Cellular and Developmental Biology, University of Rome "La Sapienza," 00185 Rome, Italy.

Journal of Virology, January 2004, p. 1020-1025, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.1020-1025.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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