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Gene Expression Patterns Induced by HPV-16 L1 Virus-Like Particles in Leukocytes from Vaccine Recipients

  1. Author:
    Garcia-Pineres, A. J.
    Hildesheim, A.
    Dodd, L.
    Kemp, T. J.
    Yang, J.
    Fullmer, B.
    Harro, C.
    Lowy, D. R.
    Lempicki, R. A.
    Pinto, L. A.

  2. Author Address

    Garcia-Pineres, Alfonso J.; Kemp, Troy J.; Pinto, Ligia A.] NCI, Sci Applicat Int Corp Frederick, HPV Immunol Lab, Frederick, MD 21702 USA. [Hildesheim, Allan] NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Dodd, Lori] NIH, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Yang, Jun, Fullmer, Brandie, Lempicki, Richard A.] NCI, SAIC Frederick, Lab Bioinformat & Immunopathogenesis, Frederick, MD 21702 USA. [Harro, Clayton] Johns Hopkins Univ, Ctr Immunizat Res, Baltimore, MD 21205 USA. [Lowy, Douglas R.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
    1. Year: 2009
  2. Journal: Journal of Immunology
    1. 182
    2. 3
    3. Pages: 1706-1729
  4. Type of Article: Article
  1. Abstract:

    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 Journal of Immunology, 2009, 182: 1706-1729.

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External Sources

  1. PMID: 19155521

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