HKU discovers a novel DNA vaccine which can induce a high frequency of CD8+T cells to combat Aids
A new strategy for designing AIDS vaccine
15 May 2013
AIDS remains an incurable deadly disease up to date with neither an effective vaccine nor a therapeutic cure. Over the past 30 years, although scientists have long been devoted to the research of how to induce a high frequency of qualitatively improved CD8+T cells (The function of CD8+T cells is to eliminate HIV infected cells) for the purpose of AIDS prevention and treatment, few groundbreaking advancements have been achieved. The AIDS Institute of The University of Hong Kong Li Ka Shing Faculty of Medicine lately discovers specific molecule on dendritic cells (DC) which can induce a high frequency of anti-HIV CD8+T cells. It is believed that the findings could be served as a new strategy for designing AIDS vaccine as well as other vaccines against cancer, bringing hopes of survival. The study on new vaccine has already obtained the international patent, signifying that Hong Kong researchers have the capability to invent novel AIDS vaccine. The study has recently been published in the prestigious international science journal, Journal of Clinical Investigation.
The leading scientist of the study, Dr Chen Zhiwei, Director of the AIDS Institute, The University of Hong Kong Li Ka Shing Faculty of Medicine says, “After four years of tremendous efforts, our team has successfully developed a novel DNA vaccine validated in mouse challenge models. By presenting HIV-1 GAG p24 antigen through the interaction between PD1 and its receptor PD-L1/L2 on DC, DC is stimulated. It is thereby more effective in transferring antigen to the T cells and results in high levels of qualitatively enhanced and long-lasting HIV-specific CD8+ T cells for killing and removing virus infected cells and for protection. If the vaccine works on humans in the future, it will be significant not only for preventing HIV infection but also for immunotherapy for the treatments to 30 million infected cases in the world. It is hoped that AIDS could be eliminated.”
Research implications
The study brings new insights to AIDS vaccine design. Dr Chen Zhiwei emphasises, “With this pioneer discovery, we have already obtained the international patent, implying that we have the capability to invent novel AIDS vaccine in Hong Kong. If the vaccine works on humans, it will be a great leap forward not only for preventing HIV infection but also for immunotherapy for treating infected cases in the world.” Besides, the study could also be taken reference for designing vaccine for other diseases, such as cancer vaccine, leading to the immunotherapy for cancer in the future.
Research method and results
Researchers first construct the novel DNA vaccine by combining PD1 with HIV-1 GAG p24 antigen and then administer into the mice intramuscularly through in vivo electroporation. The immunisation regimen consists of a prime and two boosts three weeks apart. Two weeks after the final boost, the immune responses of HIV-1 GAG p24 antigen are measured using various assays. The team finds that anti-HIV CD8+ T cells responses are markedly elevated compared to the control group, which receives conventional p24 DNA vaccine.
Upon further examination, for the novel DNA vaccine, not only the CD8+ T cells have been highly induced, but also they can release more kinds of cytokines. Besides, the memory responses of these CD8+ T cells are enhanced, suggesting that the protective immunity could be prolonged. The study also demonstrates that the new vaccine could provide protection against vaccinia-GAG virus lethal challenges in mice.
Last but not the least, by the interaction between PD1 and its receptor PD-L1/L2 on DC for p24 delivery, the targeted DCs uniquely engage the antigen cross presentation pathway (which enhances the direct antigen presentation to CD8+ T cells via MHC-I molecule) while release more auxiliary cytokines (e.g. IL12), thus enhancing the amount and quality of CD8+ T cells for fighting against HIV infected cells.
Research Team
The study is led by Dr Chen Zhiwei, Director of the AIDS Institute of The University of Hong Kong Li Ka Shing Faculty of Medicine. Other key researchers include Professor Yuen Kwok-yung, Chair Professor of Infectious Diseases, Department of Microbiology, Ms Zhou Jingying, a final-year PhD candidate, Dr Li Liu and Dr Allen Cheung Ka-loon. The team is now collaborating with other parties to use the new method to study universal influenza vaccine.
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The leading scientist of the study, Dr Chen Zhiwei, Director of the AIDS Institute, The University of Hong Kong Li Ka Shing Faculty of Medicine says that their team has successfully developed a novel DNA vaccine validated in mouse challenge models, leading to a high levels of qualitatively enhanced and long-lasting HIV-specific CD8+ T cells for killing and removing virus infected cells and for protection.
The study is led by Dr Chen Zhiwei, Director of the AIDS Institute of The University of Hong Kong Li Ka Shing Faculty of Medicine (Middle), and other key researchers including Dr Allen Cheung Ka-loon (Right), Post-doctoral Fellow and Ms Zhou Jingying (Left),a final-year PhD candidate.
The graph illustrates the design of novel AIDS DNA vaccine.
The graph illustrates the mechanism of novel AIDS DNA vaccine.