【Animal Modeling】-How to build a mouse model for vaccine research


  Scientists rely on a variety of animal models, including mice, to produce human antibodies through genetic engineering of B cell receptors (a special antibody that binds to B cell membranes), thereby developing vaccines and studying human immune responses. However, these mice usually take years to develop and require complex genetic modification and careful reproduction.

   Dr. Facundo Batista, deputy director of MIT MGH and Harvard University's Lagon Institute, said: We know we need a method that can greatly speed up this process, such as CRISPR/Cas9.

   The Batista team has greatly shortened this timeline by developing a new method for generating mouse strains for preclinical vaccine evaluation. In a recent study published in the journal EMBO, this single-step method using CRISPR/Cas9 technology can produce mice with genetically engineered human B-cell receptors in just a few weeks. To test this technology, the researchers modified mice to have human B-cell receptors, which are the precursors of so-called broadly neutralizing HIV antibodies. Although these antibodies are known to be effective against HIV, it is difficult to stimulate them through vaccination. The precursors respond to antigens currently used in clinical HIV testing by generating broadly neutralizable antibody-like mutations. The ability to quickly assess the ability of various antigens to activate these precursors has the potential to significantly accelerate vaccine development. The modified B cells not only produce high-quality antibodies, but some cells have become memory cells. The production of antibodies against pathogens can maintain long-term immunity. This means that these mice can be used to quickly verify good vaccine candidates against HIV and other pathogens. The first author of this paper, Dr. Wang Xuesong, a Lagon researcher, said: "This new technology has the potential to greatly accelerate the research speed of scientists who study the evolution of vaccines and antibodies.