Gene expression patterns induced by HPV‐16 L1 VLP in leukocytes from vaccine recipients

Abstract

To determine the cellular pathways induced by an HPV‐16 L1 VLP vaccine, we compared the gene expression signature in L1 VLP‐stimulated PBMC from 19 vaccine and 7 placebo recipients before vaccination, and 1 month after receiving the second immunization. Cells were incubated for 72 hours with or without HPV‐16 L1 VLP before total RNA extraction. Gene expression was analyzed using the Human Genome Focus Affymetrix Array.Vaccination with HPV 16 L1 VLP was associated with a differential expression of genes in the immune/defense response, cytokine, cell signaling and cell cycle pathways in VLP‐stimulated PBMC. In addition, there was up‐regulation of genes associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and the IL‐1 receptor antagonist (IL1RN). Twenty‐two differentially expressed genes were selected for confirmation by RT‐PCR in an independent group of 9 vaccine recipients. Agreement with the microarray data was seen for most of these genes.In conclusion, microarray technology was used to identify host gene expression profiles induced by HPV‐16 L1 VLP in leukocytes from vaccine recipients. Further studies are needed to define their potential utility in prediction of HPV vaccination outcomes in clinical trials. (Funded by N01‐CO‐12400)