Researchers at Kymab, a UK therapeutic antibody platform company, The Scripps Research Institute (TSRI) and the International AIDS Vaccine Initiative (IAVI) have developed a new approach to creating a human vaccine against HIV. In a study published on September 8, 2016 in Science, they tested a significant first step for developing effective ways to immunize against the many HIV variants found worldwide.
Researchers have proposed that a successful vaccine would need to stimulate the immune system to produce diverse neutralizing antibodies, such as what happens when individuals infected with HIV produce antibodies against various HIV strains.
The challenge is that the antibodies that HIV patients produce derive from only a limited number of precursor antibody-producing cells and develop their characteristic immune properties over the course of a long-standing infection. Previous research has shown that these antibody-producing cells get activated when immunizing in particular animal models. For the first time, researchers were able to activate antibody-producing cells through immunization of an immune system.
To do this, researchers created a mouse model, called Kymouse™, with genes that were modified to mimic human antibody responses. The Kymouse model was then injected with an immunogen — a nanoparticle formed of 60 copies of a small protein that mimics the HIV virus. The HIV immunogen was designed to bind and stimulate the specific precursor cells for one class of broadly neutralizing antibodies. Researchers then observed whether or not the mouse mounted an antibody response.
The results were remarkable. An effective response was efficiently stimulated against the HIV immunogen.
The research team validated their results by sequencing genes from more than 10,000 cell samples. The genes did have the expected sequence for precursors to produce broadly neutralizing antibodies against the HIV immunogen.
This new research shows that the Kymouse model is able to produce antibodies of the type that can evolve to provide protection against virtually any strain of the HIV virus. It’s also proof that Kymouse is an effective platform not just for further discovery and testing of new vaccines against HIV, but for finding ways to improve other vaccine candidates.
According to William Schief, TSRI Professor and Director of Vaccine Design for the IAVI Neutralizing Antibody Center at TSRI, “It is a big step forward in this branch of HIV vaccine development. We have the first proof of principle that this HIV vaccine strategy and our vaccine candidate can work in a human immune system and trigger the first step in the pathway to developing broadly neutralizing and protective antibodies against the virus. It is the very sort of response we’d want to see as we test components of a future vaccine.”
Kymouse success in steps to developing HIV vaccine [press release]. Cambridge, UK: EurekAlert; September 8, 2016.