Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients

Alfonso J. García-Piñeres, Allan Hildesheim, Lori Dodd, Troy J. Kemp, Jun Yang, Brandie Fullmer, Clayton Harro, Douglas R. Lowy, Richard A. Lempicki, Ligia A. Pinto

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1706-1729
Number of pages24
JournalJournal of Immunology
Volume182
Issue number3
StatePublished - Feb 1 2009

Fingerprint

Human papillomavirus 16
Virion
Vaccination
Leukocytes
Vaccines
Gene Expression
Virus-Like Particle Vaccines
Genes
Transcriptome
Papillomaviridae
Galectin 2
Up-Regulation
Cyclin D2
Galectins
Papillomavirus Vaccines
Adaptive Immunity
Innate Immunity
Immunization
Cell Cycle
Placebos

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

García-Piñeres, A. J., Hildesheim, A., Dodd, L., Kemp, T. J., Yang, J., Fullmer, B., ... Pinto, L. A. (2009). Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. Journal of Immunology, 182(3), 1706-1729.

Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. / García-Piñeres, Alfonso J.; Hildesheim, Allan; Dodd, Lori; Kemp, Troy J.; Yang, Jun; Fullmer, Brandie; Harro, Clayton; Lowy, Douglas R.; Lempicki, Richard A.; Pinto, Ligia A.

In: Journal of Immunology, Vol. 182, No. 3, 01.02.2009, p. 1706-1729.

Research output: Contribution to journalArticle

García-Piñeres, AJ, Hildesheim, A, Dodd, L, Kemp, TJ, Yang, J, Fullmer, B, Harro, C, Lowy, DR, Lempicki, RA & Pinto, LA 2009, 'Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients', Journal of Immunology, vol. 182, no. 3, pp. 1706-1729.
García-Piñeres AJ, Hildesheim A, Dodd L, Kemp TJ, Yang J, Fullmer B et al. Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. Journal of Immunology. 2009 Feb 1;182(3):1706-1729.
García-Piñeres, Alfonso J. ; Hildesheim, Allan ; Dodd, Lori ; Kemp, Troy J. ; Yang, Jun ; Fullmer, Brandie ; Harro, Clayton ; Lowy, Douglas R. ; Lempicki, Richard A. ; Pinto, Ligia A. / Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. In: Journal of Immunology. 2009 ; Vol. 182, No. 3. pp. 1706-1729.
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