Spontaneous T cell responses to Epstein-Barr virus-encoded BARF1 protein and derived peptides in patients with nasopharyngeal carcinoma: bases for improved immunotherapy.

Immunotherapy approaches targeting Epstein-Barr virus (EBV)-encoded antigens induce objective clinical responses only in a fraction of patients with undifferentiated nasopharyngeal carcinoma (UNPC). In the present study, we have characterized the immunogenicity of the EBV-encoded BARF1 oncogene with the aim to assess whether this protein could constitute a new target antigen for immunotherapy in this setting. Spontaneous CD4+ and CD8+ T cell responses specific for the recombinant p29 BARF1 protein were detected by IFNgamma-ELISPOT in both EBV-seropositive donors and UNPC patients, but not in EBV-seronegative individuals. Using immunoinformatic prediction tools, we have selected 5 different candidate BARF1 T cell epitopes presented by HLA-A*0201. Although only one of these peptides was able to bind HLA-A2 with low affinity in the T2 stabilization assay, all 5 BARF1 nonamers readily elicited specific CD8+ T cell responses in EBV-seropositive HLA-A*0201+ donors and UNPC patients. Notably, the magnitude of CD8+ T cell responses to the whole BARF1 protein and derived A*0201 peptides was significantly higher in UNPC patients than in healthy donors. Moreover, cytotoxic T lymphocytes specific for the p2-10, p23-31, or p49-57 BARF1 peptides were easily obtained from HLA-A*0201+ donors. These cultures were not only able to lyse autologous targets loaded with the antigenic peptide, but also recognized tumor cells endogenously expressing BARF1 in an antigen-specific and HLA-A2-restricted manner. These findings, indicate that BARF1 is a particularly attractive antigen with immunogenic properties in most UNPC patients and provide valuable information to develop new strategies to improve the efficacy of EBV-targeting immunotherapy of UNPC patients.

Clustering of seropositivities for sexually transmitted infections.

BACKGROUND: Serology for different sexually transmitted infections (STIs) is useful for epidemiologic studies on the spread of STIs in different populations. Studying whether seropositivities for different STIs cluster could be useful, both for development of improved serologic markers of sexual behavior in populations and for understanding how STIs may differ in terms of the dynamics of their spread. GOAL: To evaluate the degree of clustering of different STIs in relation to sexual history. STUDY DESIGN: An age- and sexual history-stratified subsample of 275 women from a survey of healthy Swedish women seeking contraceptive advice was tested for human papillomavirus (HPV) types 6, 11, 16, 18, and 33; Chlamydia trachomatis; herpes simplex virus 2 (HSV-2); and human herpesvirus 8. RESULTS: Significant clustering was observed only for HPV types 6 and 11; for HPV types 16, 18, and 33; and for C trachomatis and HSV-2. The serologic marker that correlated best with lifetime number of sex partners was HPV type 16 (odds ratio [OR], 10.2; 95% CI, 3.8-27.6). The combined serologic marker that correlated most highly with sexual history was joint positivity for HPV types 16 and 33 (OR, 25.5; 95% CI, 5.4-120.4). CONCLUSIONS: The degree of clustering between different STIs varies from nonexistent to strong, implying that different STIs commonly have very different transmission dynamics. Certain combinations of STI serologic tests may be useful in epidemiologic studies for predicting sexual behavior in groups.