Basic Research on development of HPV vaccine for prevention of cervical cancer

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1.Amino acid (aa) 108-120 of L2 protein of HPV16 contains a cross-neutralization epitope against genital HPV. We designed a placebo-controlled trial in healthy adults to evaluate the safety and immunogenicity of a synthetic peptide consisting of the aa 108-120 of HPV 16 L2(L2-108/120) region. A total of 13 volunteers were given nasal inoculations with 0.1 (n=5) or 0.5mg (n=5) doses of the peptides or placebo (n=3) without adjuvant at weeks 0, 4, and 12. Sera were collected before inoculation and at 6, 16 and 36 weeks. The inoculation generated anti-L2 antibodies binding to both HPV16 and 52 L1/L2-capsids in four of the five recipients in the 0.5mg group. Sera of the four recipients showed neutralizing activities against HPV16 and 52. This study suggests the L2-108/120 peptide is tolerable in humans and has the potential as a broad-spectrum prophylactic vaccine against genital HPV2.To investigate the association between E6 variants and HLA polymorphism within a Japanese population, 55 women with HPV 16-positive cervical cancer were analyzed for E6 sequence variation and its relationship to HLA class II alleles. Compared with local controls (n=138) and published controls (n=916), DRB1*1501 and DQB1*0602 frequencies were significantly increased among patients with HPV 16 E6 prototype (n=11). Additionally, DRB1*1502 was positively associated with a particular E6 variant designated D25E (n=25), although we could not find a significant association between HLA class II alleles and L83V variant (n=16). Our doservations suggest that a specific match between E6variant proteins and HLA types may contribute to HPV16-related cervical carcinogenesis