By Sarah Kiefer
It only takes a quiet walk through the Missouri woods to encounter ticks. As they crawl from the rich vegetation among the bushes and grass onto humans and animals alike, they wreak havoc on their hosts by passing on disease causing bacterial pathogens.
One of those pathogens known to cause a 100-year-old disease is Rocky Mountain Spotted Fever (RMSF). University of Missouri scientist, Roman Ganta, hopes to understand its inner workings to one day develop a vaccine against it.
Like several tick-borne pathogens belong to rickettsial bacteria, such as Ehrlichia Anaplasma, and Rickettsia species that cause severe diseases in various vertebrate animals, including people. Ganta has been investigating and developing vaccines against important tick-borne diseases that cause Anaplasmosis, Ehrlichiosis and RMSF in people, companion animals and agricultural animals.
“We are doing basic research first because it has to be translational, so we cannot continue without first understanding the fundamentals of the root cause of a disease,” said Ganta, a Bond Life Sciences Center principal investigator and McKee endowed professor of veterinary pathobiology. “Then we can apply that understanding to develop prevention methods to make the environment healthier and improve lives.”
RMSF is one of the most dangerous tick-borne diseases and without treatment, it can lead to death in a portion of the infected. RMSF gets its name from the red spots that appear on a patient’s skin due to damaged blood vessels. These spots can swell the arms, legs, face, and body, causing difficulty breathing and other complications. The bacterium Rickettsia rickettsii is primarily transmitted from an infected tick, although person-to-person and animal-to-animal transmission is possible.
Several tick species are known to harbor the pathogen, including the Lone Star tick (Amblyomma americanum) which has widespread distribution in Missouri and several neighboring and southeastern states.
Ganta’s research builds toward vaccines to protect against a number of tick-borne diseases.
The Ganta lab picks apart each individual gene of pathogenic rickettsial bacteria transmitted by ticks in causing diseases to identify whether it is essential for pathogens’ survival in ticks, vertebrate animals, or both.
“We expected that all the genes for the vertebrate host would be equally essential for the tick, but that was not the case,” Ganta said. “Only a small group of genes were identified as equally essential for a pathogen’s growth in a tick which was surprising.”
Armed with this knowledge, the team can build a better defense against tick-borne rickettsial diseases.
“Because we now know what proteins are essential, we can create enhanced strategies for drug and vaccine development in promoting the health of people, companion and agricultural animals,” he said.
National Institutes of Health (NIH) funding helps him work on multiple vector-borne disease vaccine projects such as RMSF, Ehrlichiosis and Anaplasmosis. A vector refers to an organism—often a blood-sucking insect or tick—that carries a pathogen from one animal to another. Those pathogens are responsible in causing diseases like RMSF, Ehrlichiosis, Anaplasmosis, and Lyme disease.
To successfully infect a vertebrate host, the pathogens have developed ways to avoid rejection and hang on to their hosts. The pathogens derive nutrients from the hosts to support their survival. While scientists don’t entirely understand what benefit ticks get out of a pathogen, Ganta looks for clues in how the genes in a pathogen change their protein expression in vertebrate hosts and ticks. He wants to understand the gene expression of pathogens during their growth in ticks and vertebrate hosts so that he can identify what the pathogen needs to survive and use that knowledge to craft a vaccine specific to each pathogen.
“How the proteins are expressed differently provide us with the whole story of what is essential for a pathogen in a tick and what is essential for it in a vertebrate host. Once we know that, the next step is to see what happens if you take those essential proteins out of those pathogens,” Ganta said. “Do the bacteria die or do they survive and grow differently in one host versus another? That’s what we investigate.”
Ganta has been pursuing this line of research for over 15 years with the continuous NIH grant support that began in 2007. His work on the RMSF vaccine project started as part of a $3.7 million NIH grant in August 2021 when he was a professor at Kansas State University (KSU). He has since continued it after his move to MU in early 2023.
Ganta’s vaccine projects on Ehrlichia and Anaplasma species pathogens started with an additional $3.2 million NIH grant that began in June of 2020 at KSU and has since been transferred to MU. Ganta’s research success has been creation of vaccines that are 100% effective in protecting dogs from the devastating diseases;RMSF and Ehrlichiosis, and Anaplasmosis in cattle. RMSF vaccine results were published in a paper in 2019, while Ehrlichiosis and Anaplasmosis vaccine work were published in 2015 and 2022, but this kind of vaccine research is yet to be extended to humans.
Ganta feels that improving the health of companion and agricultural animals will have a positive impact on the health and well-being of people. Ganta’s current focus is to test how long a vaccine protection will last and if the vaccines protect against infection in all areas of the world where the diseases are widespread.
“If these vaccines don’t protect for a long period of time, what do we do next? We have to find a better solution to extend the immunity, such as offering a booster vaccination or modify the vaccines to offer protection against distinct pathogen strains,” Ganta said.
Ganta’s RMSF vaccine is a whole-cell antigen inactivated vaccine, while Ehrlichiosis and Anaplasmosis vaccines are based on modified live attenuated bacteria. These approaches take the entire “cocktail” of proteins from the bacteria to trigger immune responses in patients without causing diseases.
“What do you do when you go to Alaska in the wintertime? You put on a coat. What do you do when you go to the Caribbean in the summertime? You wear something more comfortable for the hot weather. That process is called adaptation, and pathogens in ticks and vertebrate hosts do the exact same thing, adapting to different host environments” Ganta said.
Because pathogens constantly evolve, the vaccines must be able to handle those changes. Currently, Ganta and his team are fine-tuning vaccine variations for RMSF, so that the vaccine works against different strains of the bacteria and to define the length of protection in animals. Similarly, his team has been investigating and improving the vaccines against Ehrlichiosis and Anaplasmosis.
The team’s active modified live vaccines against tick-borne infections from Ehrlichia and Anaplasma pathogens are also effective in preventing the diseases such as Ganta’s modified live vaccine that has been effective in preventing canine ehrlichiosis and bovine anaplasmosis.
His research with the USDA grant support has been attempting to define pathogenesis with a far-reaching goal to develop a vaccine against a foreign animal tick-borne disease caused by Ehrlichia ruminantium. This pathogen results in heartwater disease in sub-Saharan Africa and parts of the Caribbean in both domestic and wild ruminants and can cause up to 80% fatalities in livestock population if introduced into the U.S. accidentally.
Ganta hopes that his continued vaccine research will one day help minimize several tick-borne diseases impacting people, companion animals and food animals.
The paper, titled “Multiple Ehrlichia chaeffeensis genes critical for persistent infection in a vertebrate host are identified as nonessential for its growth in the tick vector; Amblyomma Americanum” was published in June 2023 in Frontiers in Cellular and Infection Microbiology, detailing the genes that the Roman Ganta lab identified as essential and nonessential for the pathogen’s growth in a tick. The paper on the RMSF vaccine development and efficacy in dogs, titled “Rickettsia rickettsii Whole-Cell Antigens Offer Protection against Rocky Mountain Spotted Fever in the Canine Host” was published in 2019 in the American Society for Microbiology Journals. The work Ganta has done on Ehrlichia and Anaplasama was published in 2015 in the in the American Society for Microbiology Journals titled “Attenuated Mutants of Ehrlichia chaffeensis Induce Protection against Wild-Type Infection Challenge in the Reservoir Host and in an Incidental Host” and 2022 in the Public Library of Science (PLOS) “Targeted mutagenesis in Anaplasma marginale to define virulence and vaccine development against bovine anaplasmosis.”