GHP September 2016

56 | ghp September 2016 Research & Development Kymouse™, Kymab’s Human Antibody Discovery Platform, Successfully Demonstrates Steps to Developing HIV Vaccine The publication presents new findings from a collab- oration between researchers at Kymab, The Scripps Research Institute (TSRI) of San Diego, California, and the International AIDS Vaccine Initiative (IAVI). HIV is one of the most intransigent targets for vaccine devel- opment, and no effective vaccine has been developed in thirty years of global research. The paper is entitled “Priming HIV-1 broadly neutralizing antibody precur- sors in human Ig loci transgenic mice”. The research, which tested the first step in an ap- proach to develop effective vaccines against the range of HIV variants existing worldwide, was published in Science on Thursday 8 September 2016, and was supported by funding from the International AIDS Vac- cine Initiative and the US National Institutes of Health. The results show that Kymouse, which is a mouse that has been modified to mimic human antibody respons- es, is an effective platform for discovering and testing possible vaccines and suggest ways in which testing of vaccine candidates can be improved. “We increasingly recognise that traditional vaccine strategies will not be successful against all viruses, especially not HIV. Together with the Kymab team, we have taken a novel approach in which we have induced human antibodies in Kymouse that are at the beginning of the pathway to protective antibodies and which is a huge boost to our mission to develop a HIV vaccine.” says Dennis Burton, chair of the TSRI Department of Immunology and Microbial Science and scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center (NAC) at TSRI and the National Institutes of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID). The work is based on the observation that a fraction of people who become infected by HIV develop broadly neutralising antibodies against diverse HIV strains. Such antibodies would be ideal to protect against or possibly treat HIV infection — if a vaccine could be made to elicit them. However, these antibodies originate from a limited number of precursor antibody-producing cells in the body and acquire their unusual and protective prop- erties only during a long course of infection. Moreover, although these cells have been activated when immu- nising certain biased animal models, this is the first time it has been achieved through immunisation of an immune system, as in the Kymouse, that resembles the human. The researchers injected Kymouse strains with a na- noparticle formed of 60 copies of a small protein that mimics HIV and was designed to bind and stimulate the specific precursor cells for one class of broadly neutralising antibody. They expected to find just one such precursor cell (among tens of millions of such cells) in each immunised mouse. The research team then looked to see whether or not the mice had mounted an antibody response to this injection. Given the combined challenges of a complex immunogen structure and the rarity of the right antibodies, an effective response against the HIV immunogen was elicited remarkably efficiently. “Our phenomenal results with the teams at TSRI and IAVI came from work at the boundaries of protein engineering, immunology and vaccine technology,” explains Professor Allan Bradley, chief technical of- ficer at Kymab and director emeritus of the Wellcome Trust Sanger Institute, who developed the Kymouse platform. “Using Kymouse, we show how an advanced vaccine candidate can search out the one cell among tens of million antibody-producing cells and make it proliferate. Kymab, the Cambridge-based antibodies-to-medicines com- pany, recently announced a publication of a new approach to developing a human vaccine against HIV in the internationally renowned scientific journal Science.