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Các epitope T cell đặc hiệu với polymerase virus viêm gan B chuyển dịch trong mô hình chuột nhiễm trùng mãn tính
Tóm tắt
Nhiễm viêm gan B mãn tính (CHB) là một vấn đề sức khỏe cộng đồng đáng kể có thể được hưởng lợi từ việc điều trị bằng các chất điều chỉnh miễn dịch. Ở đây, chúng tôi mô tả một tập hợp các vắc-xin HBV điều trị nhắm vào các protein virus nội tại. Các vắc-xin được truyền bằng các vectơ adenovirus tinh tinh (AdC) thuộc kiểu huyết thanh 6 (AdC6) và 7 (AdC7) sử dụng trong chế độ tiêm chỉ hoặc chế độ tiêm lần đầu và tăng cường. Các kháng nguyên HBV được gộp vào một chất ức chế điểm kiểm tra tế bào T sớm, glycoprotein D (gD) của virus herpes simplex (HSV), điều này tăng cường và mở rộng phản ứng tế bào T cluster of differentiation (CD8)+ được gây ra bởi vắc-xin. Kết quả của chúng tôi cho thấy rằng các vắc-xin có tính miễn dịch cao ở chuột. Chúng kích thích phản ứng tế bào T CD8+ mạnh mẽ nhận biết nhiều epitope. Phản ứng tế bào T CD8+ tăng lên sau khi tăng cường, mặc dù độ rộng vẫn tương tự. Ở chuột, những con mang tải lượng HBV ổn định cao do nhiễm gan với vectơ virus liên quan adenovirus (AAV)8 biểu hiện genome 1.3HBV, phản ứng tế bào T CD8+ với các vắc-xin giảm đi kèm với sự thay đổi rõ rệt trong hồ sơ nhận diện epitope của tế bào T CD8+. Dữ liệu của chúng tôi cho thấy rằng ở các dòng chuột khác nhau bao gồm cả những dòng mang kháng nguyên phức hợp tương hợp mô người chính (MHC) lớp I, các vắc-xin HBV được phối hợp với một chất ức chế điểm kiểm tra kích thích phản ứng tế bào T CD8+ HBV mạnh mẽ và rộng rãi, và phản ứng tế bào T CD4+ thấp nhưng vẫn có thể phát hiện. Các phản ứng tế bào T CD8+ bị giảm và tính đặc hiệu epitope của chúng thay đổi ở chuột có sự tiếp xúc mãn tính với các kháng nguyên HBV. Các ý nghĩa trong thiết kế các vắc-xin HBV điều trị được thảo luận.
Từ khóa
#nhiễm viêm gan B mãn tính #vắc-xin HBV #tế bào T CD8+ #epitope #liệu pháp miễn dịchTài liệu tham khảo
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