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Clinical and Vaccine Immunology, August 2007, p. 984-989, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00090-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cytokine and Chemokine Profiles following Vaccination with Human Papillomavirus Type 16 L1 Virus-Like Particles{triangledown}

Alfonso García-Piñeres,1 Allan Hildesheim,2 Lori Dodd,3 Troy J. Kemp,1 Marcus Williams,1 Clayton Harro,4 Douglas R. Lowy,5 John T. Schiller,5 and Ligia A. Pinto1*

HPV Immunology Laboratory, SAIC-Frederick, Inc./NCI-Frederick, Frederick, Maryland,1 Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, Maryland,2 Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Institutes of Health, Bethesda, Maryland,3 Johns Hopkins University, Baltimore, Maryland,4 Center for Cancer Research, National Institutes of Health, Bethesda, Maryland5

Received 21 February 2007/ Returned for modification 18 April 2007/ Accepted 11 June 2007

To determine the systemic cytokine pattern induced by vaccination with human papillomavirus (HPV) L1 virus-like particles (VLP), we analyzed 22 different cytokines in culture supernatants of L1 VLP-stimulated peripheral blood mononuclear cells from vaccine (n = 19) and placebo (n = 7) recipients at months 0 and 2 after vaccination, using a multiplex cytokine bead array. In vaccine recipients, incubation with L1 VLP in vitro led to a statistically significant increase in production of Th1 (granulocyte-macrophage colony-stimulating factor, interleukin-2 [IL-2], gamma interferon; P < 0.0007) and Th2 (IL-4, IL-5, IL-10, IL-13; P < 0.0017) cytokines and the chemokine IP-10 (P = 0.0021) at month 2 after immunization, compared to levels seen prior to vaccination. These responses were not seen in placebo recipients. Cytokine and neutralizing antibody responses to vaccination followed the same pattern, with the highest antibody responses seen for subjects with higher cytokine responses. Cytokine profiling studies using samples from efficacy trials may provide important information about discriminators of long-term protection against HPV.

* Corresponding author. Mailing address: NCI-Frederick, Building 469, Room 120, Frederick, MD 21702. Phone: (301) 846-1766. Fax: (301) 846-6954. E-mail: lpinto{at}ncifcrf.gov

{triangledown} Published ahead of print on 27 June 2007.

Clinical and Vaccine Immunology, August 2007, p. 984-989, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00090-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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