GIBH organizes the\"Pearl River Forum: Symposium of AIDS Vaccine\"

Professor Zhiwei CHEN of Hong Kong University introduced their work on vaccinia-based HIV vaccine in the Aaron Diamond AIDS Research Center. This attenuated vaccinia vector contains multiple HIV genes. It took them less than five years to develop the vaccine from lab to phase 1 clinical trials, the result of which shows that volunteers had good tolerance for the vaccine, having generated neutralizing antibody to gp120 and T cell immunity for five HIV genes.

Feng LI, a Ph.D. student at Dr. Ling CHEN’s lab, GIBH also gave a talk on “Multiple immunogen design for HIV vaccine and construction of a new kind of high-capacity adenovirus vector”. So far there is not a candidate HIV vaccine containing the same antigens as attenuated live SIV vaccine. By using SIV / Chinese rhesus macaque models, the protect potency of multigenes vaccine was investigated. Besides, the MHC alleles of Type I in Chinese rhesus macaque was also analyzed. The protection potency of multi-gene vaccination was compared to initially clarify the best immunogene design as the conceptual verification for the effect of the combined structural and non-structural protein vaccination. A new complementary high-capacity adenovirus vector system has been successfully constructed.

Professor Paul Zhou of Institut Pasteur of Shanghai, Chinese Academy of Science, absent from the Symposium, has asked Dr. Xin MA of GIBH to introduce his work from three aspects: the strategy for developing membrane-bound antibody-based AIDS prevention and therapy, pseudotyped viral -based immunogens for vaccine against HIV and the establishment the model of humanized SCID mouse. The other reports at the Symposium include “Malaria parasite-based vector for vaccine against HIV” by Professor Xiao-ping CHEN of GIBH; ” the strategy to retain the immunity response of T cell and antibody stimulated by HIV vaccine” by Professor Chang-you WU of SUN Yat-sen University; and “HSV-based vector for vaccine against HIV” by Professor Tao PENG of GIBH.  There was a very warm discussion during the meeting about these topics.

  

The participants at the symposium agreed on that there is still a long way before successful AIDS vaccines is developed, the science and pharmaceutical industry should adjust their strategies in accordance with time. The data should be analyzed thoroughly after merck halted its AIDS vaccine clinical trials, so as to further explore AIDS vaccine development in several directions. The meeting reached the following consensus: Firstly, the development of efficacious AIDS vaccine remains an international problem. Since the HIV was identified in 1981, three stages in AIDS vaccine development have been going through. The AIDS vaccine based on neutralizing antibody has not yet been successful. As the Merck’s Phase 2b trial interim evaluation revealed, the once promising cell immunity based vaccine could not prevent infection and reduce the amount of virus in the bloodstream. Even though, we have to admit that valuable experience for immune analysis and organization of great clinical trials has been accumulated during the development procedure. Secondly, it is expected that the Merck’ data for clinical trials will soon be shared with others, and the specific reasons for vaccine failure could be identified. Thirdly, for vaccine development, we must persist in a scientific approach to development, follow the laws of the natural sciences, and avoid being blundering. We should learn from the past experience and accumulations, together with the innovative thinking, do things that others have not thought of, and things that others have not done before. Have the courage to imagine and practice. Only in this way can we achieve a breakthrough.

With regard to the design of an AIDS vaccine,  the following aspects are to be considered:

1, What kind of immune responses should we induces? An effective AIDS vaccine need to balance effective humoral immunity and cellular immunity, in addition to strengthening the cellular immune response, more attention should be paid to the induction of antibody response. At the same time, it should also be taken into account how to balance the systemic immune response and mucosal immune response.

2, The selection of vaccine sectors. So far, it seems that the adenovirus has a strong adjuvant effect. But the mechanism of adenovirus immune response induced should be further explored, and the vector genome should be improved to remove a component of unwanted immune response. As a another common vector, it is also necessary to reduce the side effects Pox virus vector in AIDS vaccine research. In addition, other types of vectors, such as HSV vector or Plasmodium vectors should be developed.

3, The immunization strategy. More attention is needed for the biological characteristics of various types of AIDS vaccine vector. At present, the vector vaccines, DNA vector vaccine protein vaccine used alone or in combined use are adopted as the main immunization strategy. A single immunization approach may not be effective in inducing immune protection. And the ideal combination of the vector combination needs to be further explored. The Specific areas include: immunization sites, different prime and boost, immune dose of boost, other vaccine vector development, the use of adjuvants. At the same time the feasibility for future vaccine production should also be considered during the design and development of vaccines.  

4, The selection of antigen. The current main choice of antigen are Gag, Pol and Nef. Some researchers also add the env. At present, there is no result showing that effective immune protection could be induced. Research should be done with HIV all protein as antigens. Among which, the optimization and reconstruction of antigen gene should be involved. In addition, it is also necessary to find out the conservative epitope, with the hope of developing effective epitope.

5. The development of more predictable animal models, in particular non-human primate models. And to choose appropriate animal models and complete the full pre-clinical evaluation. Currently, the model in use of Indian rhesus monkeys is most widely adopted in the pre-clinical evaluation of the effectiveness of vaccine, and the challenging virus is mainly monkey immunodeficiency virus (SIV) and the chimeric HIV virus SHIV, SIVmac239, SIVmac251, and so on. But pathogenic SHIV may not accurately reflect the human infection with the HIV disease process. SHIV might just be "a sheep dressed in the wolf cloak of HIV ", i.e., SHIV can be easily controlled by the immune system, without being able to reflect the true effectiveness of vaccine protection. Thus the protective effect on animal model is not exactly the same as on human beings. Linked to the geological advantages in resources in South China, detailed analysis of the course of diseases and immune responses of SIV infected Chinese rhesus model is necessary, so as to build up the SIV Chinese rhesus model and serve the HIV vaccine research.

6, Strengthening exchanges and cooperation. Firstly, direct cooperation among the experts at the conference should be established. Secondly, interdisciplinary cooperation with experts of immunology is required to update and deepen the understanding of the immune system. To obtain a great deal of clinical trials data for vaccine research and development is essential. At the same time, exchanges and communication should be accelerated between domestic and foreign counterparts and the International AIDS Vaccine Initiative Organization(IAVI), the United States National Institutes of Health (NIH), the Merck company , and other international organizations and large corporations, with the joint efforts for an early solution to AIDS.