While tackling COVID-19, Texas Biomed never lost sight of the world’s most notorious killers: HIV, tuberculosis and malaria.
When COVID-19 arrived on the scene, the Texas Biomed team knew that as an infectious disease research institute, it had a significant role to play. Many put aside their life’s research in order to focus all expertise, lab space and resources to develop critical animal models needed to understand the virus and develop vaccines and treatments.
“It’s what you do when in a crisis,” says Professor Jordi B. Torrelles, PhD, a tuberculosis investigator who was tapped to help coordinate Texas Biomed’s COVID-19 research efforts. “Everybody was predisposed to move quickly, to find solutions.”
Now, as variant waves ebb and flow, some researchers are staying focused on COVID-19 and others have picked back up where they left off with renewed urgency and determination. Other leading infectious killers plaguing humanity — HIV, tuberculosis (TB) and malaria — have not gone away during the pandemic. In fact, they’ve gotten worse.
Global health experts are estimating the pandemic reversed years of progress on these “big three” diseases, which collectively kill more than 2.5 million people annually. Across the board, the pandemic caused severe disruptions for administering vaccines, diagnostic tests and treatments, and that is translating to increases in infections and deaths.
Notably, the Global Fund reported a large 22% drop in HIV testing in the countries where it operates. While malaria control efforts continued through the pandemic, the World Health Organization (WHO) reported malaria infections and deaths still rose, and the vast majority of deaths are children under the age of 5.
TB experienced the greatest setback. Deaths rose for the first time in more than a decade to more than 1.5 million in 2020. The significant decline in diagnoses and treatments is projected to add 6.3 million infections and 1.4 million deaths from TB between 2020 and 2025, according to an analysis by the Stop TB Partnership.
“We’re in for a period of time when infectious disease threats worldwide will become an even larger force than they already are,” says Texas Biomed President/CEO Larry Schlesinger, MD. “But the collaborative spirit within the international scientific community and at Texas Biomed has built up a huge wave of momentum that we can use to tackle HIV, TB and malaria, as well as other emerging and reemerging infectious diseases.”
While COVID-19 mRNA vaccines were developed and tested within a year of the novel pathogen emerging, the vaccine technologies used were under development for decades and were adapted to this new threat. Those innovations are now being explored for HIV, TB and malaria applications; however, these complex diseases are extremely difficult to prevent and treat.
There is no vaccine for HIV. The only vaccine for TB is consistently effective only in children. The brand new malaria vaccine approved in 2021 is saving children’s lives but requires four shots and is estimated to be 30% effective in reducing deadly infection — far from ideal. Antiviral treatments for HIV have come a very long way; the virus is no longer a death sentence, but it still lurks in the body and treatments come with side effects — a vaccine and cure is the holy grail.
Much the same for active TB disease, which requires taking six to eight pills a day for months to get the easiest, drug-susceptible cases under control and it still can reactivate later if treatment fails. Drug-resistant TB requires upwards of 30 pills a day to manage the disease and side effects. Better options are needed to combat this growing drug resistance. Malaria parasites are also evolving to resist existing remedies, requiring new solutions.
“The challenges that we have to actually eradicate these diseases are incredibly huge,” says Joanne Turner, PhD, Texas Biomed’s Executive Vice President for Research. “We’ve got to take on drug resistance, new vaccine development and public health infrastructure challenges. It’s going to require really good teamwork.”
Texas Biomed is not wasting any time. Over the past two years, the Institute has expanded its expertise in these infectious diseases with new faculty, staff scientists, post-doctoral fellows, graduate students and technical staff, bringing the Institute to 400 team members.
“That we recruited some outstanding new scientists during the pandemic is noteworthy,” Dr. Schlesinger says. “We didn’t really stop, we actually continued to grow.”
The Institute is also expanding its leadership and collaborations through the establishment of two prestigious centers focused on TB and HIV.
GETTING ON TRAC
In March 2022, Texas Biomed was named one of four inaugural TB research training centers by the National Institutes of Health (NIH), along with Emory University, Johns Hopkins University and University of Washington School of Medicine.
Texas Biomed’s Interdisciplinary NexGen TB Research Advancement Center (IN-TRAC) will leverage the expertise, facilities and collaborations based at the Institute and across South Texas to provide a world-class training program for up-and-coming researchers.
Specifically, researchers will receive “bench-to-bedside” training. They will work with cells in petri dishes on basic science in microbiology and immunology, and learn what insights different animal models can offer. They will visit patients at the Texas Center for Infectious Disease in San Antonio, the only free-standing TB hospital in the U.S., and participate in field research and clinical trials at the Texas-Mexico border.
“Getting this complete picture enables researchers to ask better questions and design better experiments back in the lab,” Dr. Turner says. “This program will also help them break down perceived barriers into taking on new technologies or methods.”
NIH’s National Institute of Allergy and Infectious Diseases (NIAID) set up the IN-TRACs as part of its strategic research plan for TB. Texas Biomed competed with universities across the country to host one of the centers, and will receive a $5.8 million program grant over the next five years.
“We are thrilled NIH recognized the unique combination of resources we have in our region that make us one of the best places for TB research and training in the nation,” Dr. Schlesinger says. “This is going to be transformative for the Institute, helping to attract even more talent and expand our impact on the TB field.”
GOING FAR TOGETHER
To help end the HIV/AIDS epidemic in Texas, Baylor College of Medicine, University of Texas Health Science Center at Houston and Texas Biomed joined forces to establish the Texas Developmental Center for AIDS Research (D-CFAR).
By improving collaboration and communication among a network of researchers, health providers and community members, the center aims to optimize HIV/AIDS research, find new ways to treat the disease and reduce infections across Texas and the Southern United States.
“Texas is exceptional for all the wrong reasons when it comes to HIV/AIDS,” explains Texas D-CFAR Director Thomas Giordano, MD, of Baylor College of Medicine. Texas had the third-highest number of new HIV diagnoses in 2019, behind only Florida and California. More than half of HIV diagnoses in the nation are in the Southern region, despite that area having only 38% of the country’s population.
In June 2021, NIH provided a $5 million grant to launch the Texas D-CFAR, which is one of 17 centers nationwide.
“Texas Biomed brings both a deep bench in HIV/AIDS researchers, but also the critical nonhuman primate models needed for basic understanding of the disease and treatments,” says Deepak Kaushal, PhD, who directs Texas Biomed’s Southwest National Primate Research Center, and serves as a Texas D-CFAR co-director.
Like the IN-TRAC, a key feature of the D-CFAR is to support early-career researchers so they can be successful, including through small pilot grant funding. Riti Sharan, PhD, a Texas Biomed Staff Scientist in Dr. Kaushal’s lab, received one of the first four pilot grants from the Texas D-CFAR for her HIV and TB co-infection research. Dr. Sharan was one of those researchers who dropped everything to help with COVID-19 studies due to her expertise working with animal models and in biosafety level 3 laboratories, and has since been able to refocus on TB and HIV.
“It’s an incredible feeling that through our teamwork across the Institute, we had a direct impact on the development of COVID-19 animal models and vaccines,” she says. “And now it is even more imperative to accelerate preclinical studies for TB and HIV therapies and vaccines.”
EVER EVOLVING PARASITES
Malaria and other parasite research continued at Texas Biomed throughout the pandemic. While fewer people could be in the lab at the same time, they did not have to stop work. This was especially important for Professor Tim Anderson, PhD, who studies the genetics of malaria parasites and tiny flatworms called schistosomes that cause the neglected tropical disease schistosomiasis. He and his team maintain the entire life cycle of schistosomes in the lab and these parasites have unique genetic variations that only exist at Texas Biomed.
“If we go away for a week, everything will be dead and we’ve lost years and years of research,” Dr. Anderson says. “Stopping work during the pandemic was not an option.”
That continued effort — while also helping with genetic sequencing for COVID-19 studies at the Institute — has paid off. Over the past two years, the lab made significant progress on the genetic underpinnings of drug resistance in both malaria parasites and schistosomes. A key feature of this work is studying how pathogens evolve, which Dr. Anderson notes has been front page news throughout the pandemic as the SARS-CoV-2 virus mutates to escape vaccines and treatments.
But while the world is currently thinking about one particular infectious disease, he is worried that as the pandemic fades, heightened interest and investment in infectious disease research will too.
“COVID has really taught us you can make enormous progress in a very short amount of time if, essentially, you throw money and enthusiasm at the problem,” Dr. Anderson says. “There are a host of other infectious diseases that are killing millions of people year in, year out. With the same money and enthusiasm, we can deal with these problems. We could have a world without HIV, TB and malaria.”
This story appeared in the Summer 2022 edition of TxBiomed magazine. See more stories from TxBiomed here.