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Journal of Virology, August 2002, p. 7832-7842, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7832-7842.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Priming of Human Papillomavirus Type 11-Specific Humoral and Cellular Immune Responses in College-Aged Women with a Virus-Like Particle Vaccine

Rebecca T. Emeny,1 Cosette M. Wheeler,1* Kathrin U. Jansen,2 William C. Hunt,1 Tong-Ming Fu,2 Judith F. Smith,2 Stefani MacMullen,2 Mark T. Esser,2 and Xavier Paliard2

Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico,1 Virus and Cell Biology, Merck Research Laboratories, Merck and Co., Inc., West Point, Pennsylvania2

Received 25 January 2002/ Accepted 30 April 2002

In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12. All vaccine recipients had positive HPV-11 VLP-specific lymphoproliferative responses at month 3 following the second immunization (geometric mean lymphoproliferative stimulation index [SI] = 28.4; 95% confidence interval [CI] = 16.9 to 48.0) and HPV-11 VLP-specific antibody titers following the first immunization at month 1 (geometric mean antibody titer = 53.9 milli-Merck units/ml, 95% CI, 34.8 to 83.7). In contrast, lymphoproliferative and antibody titer responses were never detected in the participants who received placebo. Relatively homogeneous lymphoproliferative responses were observed in all vaccinated women. The mean lymphoproliferative SI of the vaccinated group over the first 12 months of the study was 7.6-fold greater than that of the placebo group following the initial immunization. The cellular immune responses generated by VLP immunization were both Th1 and Th2, since peripheral blood mononuclear cells from vaccinees, but not placebo recipients, secreted interleukin 2 (IL-2), IL-5, and gamma interferon (IFN-{gamma}) in response to in vitro stimulation with HPV-11 VLP. The proliferation-based SI was moderately correlated with IFN-{gamma} production and significantly correlated with IL-2 production after the third immunization (P = 0.078 and 0.002, respectively). The robust lymphoproliferative responses were specific for HPV-11, since SIs generated against bovine papillomavirus and HPV-16 VLPs were not generally observed and when detected were similar pre- and postimmunization.

* Corresponding author. Mailing address: University of New Mexico Health Sciences Center, School of Medicine, Dept. of Molecular Genetics and Microbiology, BRF 123, 915 Camino de Salud, NE, Albuquerque, NM 87131-5276. Phone: (505) 272-9151. Fax: (505) 277-5273. E-mail: cwheeler{at}salud.unm.edu.

Journal of Virology, August 2002, p. 7832-7842, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7832-7842.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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