Science: successfully induced the immune system to produce key antibodies to resist HIV infection

December 8, 2019 / biool / - recently, in a research report published in the international journal Science, scientists from Duke University Medical Center cleared the main obstacles encountered in the development of HIV vaccine through research, and also proved effective in animal models, that is, to induce short-term antibody proliferation to become the backbone of effective anti HIV Photo source: Barton F Haynes, M.D., NIAID, said that the reason why we don't have HIV vaccine now is that the immune system can't produce special antibody types that can neutralize HIV In this study, we engineered the immune system to produce a special environment to produce appropriate antibodies Based on previous years' research results, now researchers have clarified how and when broad-spectrum neutralizing antibodies (bnabs) appear in HIV infected people, and when they can effectively block the proliferation of antibodies to inhibit the virus One is the immune system, which sees bnabs as a danger and shuts down the production of bnabs; the other is that neutralizing antibodies require rare changes in their genetic makeup, which do not occur in important B cell diversification processes In this study, the researchers tracked the mutations and then engineered an HIV protein to target the V3 glycan region on the envelope of the virus, allowing it to preferentially bind to antibodies carrying the necessary mutations Using a mouse model expressing human neutralizing antibody precursors, the researchers found that immunogens can induce B cell lineages to undergo impossible mutations to produce broad-spectrum antibodies The researcher ALT said that we can create a mouse model expressing human broad-spectrum neutralizing antibody, which can provide us with a powerful new model system, in which we can repeatedly detect experimental HIV vaccine; the bnabs of the second pedigree will experience an impossible mutation, which will combine with different regions of the outer membrane called CD4 binding site, when After the researchers reconstructed the antibody history, they developed a second immunogen After testing in non-human primates, the researchers found that the immunogen also selects the necessary mutations, which can help develop potential neutralizing antibodies at CD4 binding sites Now researchers have identified the mutations they need (which are not easily produced by the immune system) and can use them as targets to develop new vaccines, so that they can overcome the main obstacles and select the right mutation changes in bnabs precursors to develop new HIV vaccines Without proper antigen selection, researchers may need decades of vaccination to obtain effective antibodies Now, researchers can design sequence immunization to accelerate this timeline and select the required combination of functional antibody mutations In this study, the researchers elucidated the complex mechanism of inducing broad neutralizing antibodies against HIV, and the strategy of selecting specific antibody nucleotides through immunogen design may be applied to other infections that are difficult to develop vaccines in the future; in addition, the results of this study for cancer immunotherapy and autoimmunity The development of sexual disease therapy is also very important Such strategies can accurately turn on or off the function of the immune system without inducing harmful side effects In the end, the researchers said that we have learned a lot about the mechanism of B cells controlled by the immune system and how to manipulate the immune system to produce the required antibodies Based on the results of this study, we will continue to conduct in-depth research later to explore how to more effectively use the host immune system to resist HIV Original sources: Kevin O Saunders, Kevin wiehe, Ming Tian, et al Targeted selection of HIV specific antiviral infections by Engineering B cell mapping, science 06 Dec 2019: Vol 366, issue 6470, eaay7199 doi: 10.1126/science.aay7199