Given that some people infected with HIV naturally produce antibodies that effectively neutralize many fast-mutating viruses, scientists are developing a vaccine that can induce this broad-spectrum neutralizing antibody against HIV infection.
An emerging vaccine immunization strategy involves immunizing humans with a range of different synthetic HIV proteins as immunogens, allowing the immune system to produce a broad-spectrum neutralizing antibody against HIV. This strategy relies on the ability to bind and activate the first immunogen of a particular cell, a precursor B cell known as a broad-spectrum neutralizing antibody. It has the potential to evolve into B cells that produce a broad spectrum of neutralizing antibodies.
A study published in Science on March 25th has found precursor cells that produce broad-spectrum neutralizing resistant antibodies in most people, and describes gene-targeted HIV vaccines that bind to these B cells.
Discovery of broad-spectrum neutralizing resistant antibodies to B cells
The study found that almost all people have precursors to these broad-spectrum neutralizing antibodies. Even in the presence of competition with other immune cells, precisely designed proteins can bind to these cells that are prone to develop into a broad spectrum of neutralizing antibodies produced by HIV.
The body's immune system contains large libraries of different precursor B cells, so it responds to a wide variety of pathogens. But this also means that it is very rare for precursor B cells to recognize a particular feature of a viral surface throughout the B cell pool.
The challenge for vaccine developers is to determine whether the immunogen can present a viral surface that can significantly activate B cells. The study uses new techniques, and in clinical trials, most people are essentially the right combination of B cells and vaccine candidates. What is impressive is that the design of the protein can accurately bind a specific one in a million cells, indicating the feasibility of this new vaccine strategy.
In the blood donated by healthy people, the researchers found B cells that produced antibodies to the VRC01 class. Antibodies of the VRC01 class are recognized as antibodies that recognize HIV epitopes. The VRC01 class of antibodies is a group of antibodies that have been isolated from different individuals and appear to be in a very similar pathway. It is speculated that the B cells of the VRC01 class are very similar in different people.
Development of eod-gt8 60mer artificial protein vaccine
Using deep-mutation scanning and multi-target optimization, the researchers developed a gene-targeted immunogen (eOD-GT8) for the widely neutralized antibodies of the VRC01 class. Eod-gt8 60mer is an artificial protein designed to promote the production of a broad neutralizing antibody to HIV by these VRC01 class B cells.
This research work promotes Phase I clinical trials to test the artificially prepared HIV vaccine protein "eOD-GT8 60mer". The purpose of clinical research is to test the safety of this artificial protein in the human body to produce an immune response and to produce a broad spectrum of neutralizing antibodies. The results of this research work are very important for how to design doses and analytical methods for clinical trials.
In June last year, researchers have discovered that eOD-GT8 60mer is able to produce antibodies and protect against HIV in mice. If the effect is the same in humans, the extra-enhanced immunity of this antigen is thought to be necessary to produce a broad-spectrum neutralizing antigen that is resistant to HIV.
The new work also provides researchers with a way to assess whether a new antibody protein binds to its intended precursor cells. This approach is an important tool for targeted and effective AIDS vaccine design, providing targeted immunogens for testing before large, time-consuming and expensive clinical trials.
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