Colo útero HPV Microorganismos

Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses That Localize in Mucosal Lesions

Escrito por Carla Brito Lopes

About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral blood T cell responses to vaccine antigen. We report marked immunologic changes in the target lesion microenvironment after intramuscular therapeutic vaccination targeting HPV16 E6/E7 antigens, in subjects with CIN2/3 who had modest detectable responses in circulating T lymphocytes.

Histologic and molecular changes, including markedly (average threefold) increased intensity of CD8+ T cell infiltrates in both the stromal and epithelial compartments, suggest an effector response to vaccination. Postvaccination cervical tissue immune infiltrates included organized tertiary lymphoid-like structures in the stroma subjacent to residual intraepithelial lesions and, unlike infiltrates in unvaccinated lesions, showed evidence of proliferation induced by recognition of cognate antigen.

At a molecular level, these histologic changes in the stroma were characterized by increased expression of genes associated with immune activation (CXCR3) and effector function (Tbet and IFNβ), and were also associated with an immunologic signature in the overlying dysplastic epithelium. High-throughput T cell receptor sequencing of unmanipulated specimens identified clonal expansions in the tissue that were not readily detectable in peripheral blood.

Together, these findings indicate that peripheral therapeutic vaccination to HPV antigens can induce a robust tissue-localized effector immune response, and that analyses of immune responses at sites of antigen are likely to be much more informative than analyses of cells that remain in the circulation.

“From [L. Maldonado, J. E. Teague, M. P. Morrow, I. Jotova, T. C. Wu, C. Wang, C. Desmarais, J. D. Boyer, B. Tycko, H. S. Robins, R. A. Clark, C. L. Trimble, Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses That Localize in Mucosal Lesions. Sci. Transl. Med. 6, 221ra13 (2014).]. Republished with permission from AAAS.”

Sobre o autor

Carla Brito Lopes

Carla nasceu a 14 de Fevereiro de 1977 em Viana do Castelo. Completou o bacharelato em Anatomia Patológica, Citológica e Tanatológica na ESTES-Porto em 1998 e licenciou-se em 2001 pela Escola Superior de Tecnologia da Saúde em Lisboa. Concluiu a certificação em Laboratory Management pela ASCP (American Association of Clinical Pathology) em Setembro de 2016.
Actualmente encontra-se a frequentar mestrado em Genética Molecular e Biomedicina na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa.