Dr. Ippolito seeks to develop more effective vaccines and antibody treatments for a range of global health threats, including SARS-CoV-2, influenza and malaria.
SAN ANTONIO (Aug. 14, 2024) – Peering deep inside the immune system and pulling out a comprehensive list of antibodies produced in response to an infection or vaccine was once a monumental, if not nearly impossible, task. Today, with the latest technologies and approaches – including those developed by Greg Ippolito, Ph.D., and his collaborators –tens of thousands of antibodies can be identified in a single experiment.
“My antibody repertoire and your antibody repertoire are incredibly diverse and unique, like fingerprints,” says Associate Professor Ippolito, who joined Texas Biomedical Research Institute (Texas Biomed) this month after 13 years at the University of Texas at Austin. “We can now map those fingerprints at incredible resolution and find the small percentage of similarities – which we call convergent immune responses – that we can then use to make better vaccines and antibody therapies.”
Dr. Ippolito brings his passion for both fundamental and applied research to Texas Biomed. He said the Institute’s distinct approach combining preclinical research with innovation and commercialization was a main draw in his recruitment.
Texas Biomed’s Applied Science and Innovation (ASI) team directs its contract research for industry, government and other partners.
“We are thrilled Dr. Ippolito has joined Texas Biomed,” says ASI Executive Vice President Cory Hallam, Ph.D. “His lab expands our expertise and capabilities in developing new diagnostics, therapies and vaccines from within the Institute and in conjunction with industry and government partners.”
Dr. Ippolito holds a Ph.D. in microbiology from the University of Alabama at Birmingham and specializes in B-cell immunology. B cells are responsible for producing antibodies – the proteins that physically fight infections. There are 100 billion B cells in the body, all of which have various antibodies affixed to their surface membranes. Scientists can get a good look at those antibodies, which are called B cell receptors, by sequencing B cell DNA and RNA with next-generation sequencing.
But that is only half the story.
When the body encounters a bacterium, virus, parasite or other antigen (hey, allergies!), only some B cells are activated and release their antibodies to spread through the bloodstream and other fluids. These free-floating or “humoral” antibodies are variations of immunoglobulin (Ig) proteins – highly selected and optimized to combat a specific trigger. This much smaller subset of antibodies is captured through mass spectrometry, a tool used to identify proteins.
Dr. Ippolito and his collaborators optimized a protocol that combines next-generation sequencing of B cells and mass spectrometry to identify immunoglobulins found throughout the body, which they termed BCR-seq and Ig-seq, respectively.
“Those two combined – BCR-seq and Ig-seq – allow the clearest picture, in my opinion, of the complete antibody repertoire in response to any vaccine, pathogen or other antigen,” Dr. Ippolito says.
He and collaborators, including Jason Lavinder, Ph.D., at UT Austin and Ralph Baric, Ph.D., at University of North Carolina at Chapel Hill, used the approach to identify broadly effective antibodies against COVID-19. Based on those findings, the team developed several monoclonal antibodies and found one in particular that not only neutralizes the original version of SARS-CoV-2, but it also works against all variants of concern, including more recent variants. It also worked against related SARS-1 and a range of coronaviruses found in bats and pangolins – which could pose a threat if the viruses spill over and begin infecting people. The research was published this month as part of a paper in Cell Reports Medicine analyzing immune responses following both COVID-19 infection and vaccination.
“The antibodies appear to be so effective because they target more parts of the virus’s spike protein than previous antibody cocktails that no longer work,” explains Dr. Ippolito. “In our prior work published in the journal Science, Ig-seq made it quite easy to spot these extraordinary antibodies across samples from a small cohort of only four donors who had recovered from mild COVID-19 infections.”
Dr. Ippolito and Dr. Lavinder are longtime collaborators and will continue their joint research on SARS-CoV-2 as well as influenza, dengue and malaria – all infectious diseases that align with key strengths at Texas Biomed.
Notably, Drs. Ippolito and Lavinder are helping evaluate the effectiveness of an experimental malaria vaccine, called RH5, developed by Simon Draper, DPhil, at the University of Oxford’s Jenner Institute. As the vaccine progresses through clinical trials, their role is to characterize the antibody repertoire produced in people given the vaccine, including those most at risk: infants and young children. This follows similar work by Dr. Ippolito on the R21 malaria vaccine approved by the World Health Organization in October 2023.
“It is estimated that a child dies of malaria nearly every minute,” Dr. Ippolito says. “I am grateful to be a small part of this work and help tackle this ancient disease.”
Dr. Ippolito also leverages Ig-seq to study the antibody repertoire generated following dengue infection or vaccination, and in autoimmune diseases such as lupus, in which antibodies mistakenly attack healthy organs and tissues.
While continuing his own research program, Dr. Ippolito is looking forward to helping clients partnering with Texas Biomed’s Applied Science and Innovation team to test their vaccines or treatments. “It makes perfect sense,” Dr. Ippolito says. “The BCR-seq and Ig-seq platform is highly applicable to contract research and helping bring vaccines to market.”
He is excited to join Texas Biomed and the greater San Antonio research community. When the COVID-19 pandemic hit, he watched with envy as researchers at Texas Biomed with access to higher biosafety level (BSL)-3 and BSL-4 laboratories moved quickly to test vaccines and therapies using live virus.
“I felt crippled,” he says. “There was only so much we could do ourselves in BSL-2 labs and then had to stop or farm it out to a collaborator. Texas Biomed is able to conduct incisive, cutting-edge experiments that must be done to develop countermeasures to protect humanity from the deadliest pathogens that are a threat to our species.”