Exploration of immune correlates of viral clearance after PVX2 immunotherapy in patients with human papillomavirus type 16 infection and cervical intraepithelial neoplasia grade ≤1

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Immune responses correlated with clearance of human papillomavirus type 16 (HPV16) were sought in PVX2 immunotherapy-treated CIN ≤1 patients. PVX2 comprises intramuscular vaccinations with HPV16 E7-targeted pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine (3 mg, weeks 0 and 4) and HPV16 L2E7E6 fusion protein (TA-CIN; 100 µg week 8). Administering PVX2 to 12 women with HPV16+ CIN ≤1 elicited both antibody and CD8+ T-cell responses, including changes in TCR diversity, clonal expansion, and emergence of public clonotypes. HPV16 was not detected in 5/11 evaluable participants at month 6. Post-vaccination E6, E7, and L2-specific antibody titers were higher, but none correlated with clearance. Neither TCR clonal diversity/expansion nor public clonotypes were associated with HPV16 clearance. While the fractions of expanded/new clonotypes were not associated with HPV16 clearance, a higher proportion of vaccine antigen-specific reads was evident post-vaccination in those clearing HPV16. High baseline serum MCP-1 associated with HPV16 persistence, and MIP-1β trended higher post-vaccination in those clearing HPV16.IMPORTANCEHPV16 is a necessary cause of over half of all cervical cancers, and in even higher fractions of other anogenital and oropharyngeal cancers. Treatments for HPV16 infection and associated pre-cancerous lesions are needed given the disease burden and limitations of current treatments. Women with persistent HPV infections endure anxiety and stress due to frequent colposcopies, inconvenience, healthcare costs from active surveillance, and potential to transmit the virus to other sexual partners. Since a majority of patients can spontaneously clear their infections, administration of an immunotherapy may promote the elimination of otherwise persistent infections where disease can progress.

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