The Laryngoscope · 2017
Immunologic responses to a novel DNA vaccine targeting human papillomavirus-11 E6E7.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ahn Julie, Peng Shiwen, Hung Chien-Fu, Roden Richard B S, Wu Tzyy-Choou, Best Simon R
Аннотация
OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus (HPV) types 6 and 11. Although a prophylactic vaccine against RRP is available, a therapeutic vaccine is needed to treat those already infected. The objective of our study was to design and test a DNA vaccine targeting HPV11 proteins.
STUDY DESIGN: Preclinical scientific investigation.
METHODS: A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated. Immunologic response to the HPV11 CRT/E6E7 vaccine was measured by vaccinating C57BL/6 mice via electroporation and measuring CD8 + T cell responses from harvested splenocytes. A tumor cell line containing HPV11-E6E7 was created, and the ability of novel DNA vaccine to control tumor growth was measured in vivo.
RESULTS: Our vaccine generated a significant and specific CD8 + T-cell response against the HPV11-E6aa41-70 peptide. The CD8 + T-cell responses did not recognize E7 epitopes, indicating E6 immunodominance. CD8 + responses were augmented in the CRT-linked vaccine compared to a control non-CRT vaccine. The HPV11 CRT/E6E7 vaccine was used to treat mice inoculated with a HPV11 E6E7 expressing tumor cell line after temporary CD3 depletion to facilitate tumor growth. Vaccinated mice had a significantly lower tumor growth rate (P = .029) and smaller tumor volumes compared to control mice, indicating an augmented immunologic response in vaccinated mice.
CONCLUSIONS: A DNA vaccine targeting HPV11 E6E7 generates a specific HPV11 CD-8 + T-cell response capable of reducing the growth of HPV11-expressing tumors. DNA vaccines are a promising immunologic strategy for treating RRP.
LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2713-2720, 2017.
STUDY DESIGN: Preclinical scientific investigation.
METHODS: A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated. Immunologic response to the HPV11 CRT/E6E7 vaccine was measured by vaccinating C57BL/6 mice via electroporation and measuring CD8 + T cell responses from harvested splenocytes. A tumor cell line containing HPV11-E6E7 was created, and the ability of novel DNA vaccine to control tumor growth was measured in vivo.
RESULTS: Our vaccine generated a significant and specific CD8 + T-cell response against the HPV11-E6aa41-70 peptide. The CD8 + T-cell responses did not recognize E7 epitopes, indicating E6 immunodominance. CD8 + responses were augmented in the CRT-linked vaccine compared to a control non-CRT vaccine. The HPV11 CRT/E6E7 vaccine was used to treat mice inoculated with a HPV11 E6E7 expressing tumor cell line after temporary CD3 depletion to facilitate tumor growth. Vaccinated mice had a significantly lower tumor growth rate (P = .029) and smaller tumor volumes compared to control mice, indicating an augmented immunologic response in vaccinated mice.
CONCLUSIONS: A DNA vaccine targeting HPV11 E6E7 generates a specific HPV11 CD-8 + T-cell response capable of reducing the growth of HPV11-expressing tumors. DNA vaccines are a promising immunologic strategy for treating RRP.
LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2713-2720, 2017.