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* HPV Immunology Laboratory, Science Applications International Corporation (SAIC)-Frederick/National Cancer Institute (NCI)-Frederick, Frederick, MD 21702;
Division of Cancer Epidemiology and Genetics and
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Institutes of Health, Bethesda, MD 20892;
Laboratory of Bioinformatics and Immunopathogenesis, SAIC-Frederick/NCI-Frederick, Frederick, MD 21702;
¶ Center for Immunization Research, Johns Hopkins University, Baltimore, MD 21205; and
|| Center for Cancer Research, National Institutes of Health, Bethesda, MD 20814
Human papillomavirus (HPV) virus-like particle (VLP) vaccines were recently licensed. Although neutralizing Ab titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMCs from 17 vaccine and 4 placebo recipients before vaccination and 1 mo after receiving the second immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated with modulation of genes involved in the inflammatory/defense response, cytokine, IFN, and cell cycle pathways in VLP-stimulated PBMCs. Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing Ab titers were found for cyclin D2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with microarray data was seen for more than two-thirds of these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP, in particular, IFN-induced genes, was observed in PBMCs collected before vaccination, with many of these genes being further induced following vaccination. In conclusion, we identified important innate and adaptive response-related genes induced by vaccination with HPV-16 L1 VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health (N01-CO-12400).
The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
2 Current address: Escuela de Química, Universidad de Costa Rica, San José, Costa Rica.
3 Address correspondence and reprint requests to Dr. Ligia A. Pinto, Science Applications International Corporation (SAIC)-Frederick/National Cancer Institute (NCI)-Frederick, Building 469, Room 120, Frederick, MD 21702. E-mail address: lpinto{at}ncifcrf.gov
4 Abbreviations used in this paper: HPV, human papillomavirus; ds-cDNA, double-stranded cDNA; RPLPO, ribosomal protein, large P0; VLP, virus-like particles.
5 The online version of this article contains supplemental material.
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