ATLANTA – Mercer University College of Pharmacy researcher Martin D’Souza, Ph.D., says there is good news and bad news when it comes to developing a vaccine for COVID-19.
The good news: “It is extremely easy to develop vaccines, and even more so for viruses,” said Dr. D’Souza, who has served since 1986 on the faculty at Mercer, where he focuses on the design and delivery of nanovaccines for infectious diseases and cancer.
The bad news: “We, as humans, have never seen this virus before so we have no innate immunity towards it,” he added.
Perhaps, if circumstances had been different during the outbreak of the SARS-CoV-1 virus in 2002-2003, Dr. D’Souza said, we may already be very close to a vaccine for the new coronavirus, SARS-CoV-2.
However, SARS-CoV-1, which originated in China and caused a reported 774 deaths in 8,098 cases worldwide, disappeared almost as quickly as it appeared, and interest in developing a vaccine quickly waned.
“Had we developed a vaccine then, we would have been much ahead of the game now,” Dr. D’Souza said.
Still, he said, teams of researchers who were investigating SARS-CoV-1 have quickly mobilized and are able to make “educated guesses” regarding the direction of research into SARS-CoV-2.
Vaccine development begins with growing the virus in the lab and attenuating – or inactivating – it so that it becomes harmless or less virulent. The attenuated virus is then used in mice studies as researchers seek to develop antibodies in the mice’s immune system to attack the virus. Alternate methods to develop vaccines include using some antigenic protein on the virus surface to develop vaccines specific to those antigenic sites.
The key in this process is to develop memory response resulting in long-term immunity for a period of at least one year, which is why the flu vaccine, for instance, is developed and administered annually.
Once researchers are able to successfully develop antibodies in mice, studies typically proceed to include a second species such as ferrets, which have immune systems that more closely resemble those of humans. Successful trials in these animal models then clear the way for human studies.
“Designing a vaccine is rather simple,” said Dr. D’Souza. “The slow process is completing the safety studies in humans and the necessary paperwork, including the INDA (investigational new drug application) and FDA (Food and Drug Administration) approval process.”
SARS-CoV-2 vaccine research in his laboratory, Dr. D’Souza said, will focus on the Spike surface glycoprotein – also known as the S protein – that is critical to the virus attaching itself to human cells. The S protein fits perfectly into a receptor called angiotensin-converting enzyme 2, or ACE-2, on human alveolar cells in the lungs. Once the lung cells take up the virus, it effectively uses the human body to replicate itself millions of times over.
As the virus is multiplying in the lungs, the immune system releases cytokines, toxic substances it uses to kill the virus, Dr. Souza explained. While the immune system may be successful against the virus, it can also cause “cytokine storms,” which result in vascular leakage as lung cells become porous. As the body experiences pneumonia, the immune system continues to release more cytokines, in turn resulting in accumulation of even more fluid into the lungs.
“Carbon dioxide from the body cannot be exchanged, and oxygen cannot be taken into the lung cells,” said Dr. D’Souza. “This is why people need ventilators.”
Several drugs under consideration to treat the new coronavirus include remdesivir, intended to prevent the S protein from attaching to human cells; cloroquine, intended to prevent the virus from entering the process of replication; ritonavir, a protease inhibitor intended to prevent the virus from replicating; tocilizumab, intended to decrease the production of cytokines; and corticosteriods, intended to reduce inflammation in general. Remdesivir is currently in Phase 3 clinical trials, the final step toward receiving FDA approval.
The most effective treatment would be a forthcoming vaccine, something Dr. D’Souza is hopeful may be available as early as this winter if the clinical trials are successful.
“Hopefully, by the time this virus comes around in the next cycle – and we’re pretty sure it will show up in the regular flu cycle – there will be a vaccine to add to the flu vaccine to protect people,” he said.
In the meantime, Dr. D’Souza recently began his own research into using patented nanotechnology to design a microparticle vaccine for SARS-CoV-2. He has previously used this approach to conduct research on vaccines for universal influenza, RSV, HPV, meningitis and gonorrhea, as well as melanoma, breast, ovarian and prostate cancer.
Dr. D’Souza serves as professor of pharmaceutical sciences, director of graduate programs, director of clinical laboratories, co-director of the Center of Drug Delivery and Dick R. Gourley Chair of Pharmaceutics in the College of Pharmacy.
About the College of Pharmacy
Mercer University’s College of Pharmacy is ranked the top private pharmacy school in the Southeast, according to the 2020 U.S. News & World Report. The college offers doctoral degrees in pharmacy (Pharm.D.) and pharmaceutical sciences (Ph.D.). Founded in 1903 as the independent Southern School of Pharmacy, the school merged with Mercer University in 1959 and in 1981 became the first school in the Southeast to offer the doctor of pharmacy degree as its sole professional degree. In 1988, the College launched its graduate program, offering the Ph.D. degree in pharmaceutical sciences. With an enrollment today of more than 500 students and a distinguished faculty of basic scientists and clinicians, the College of Pharmacy houses four centers focusing on research, teaching and learning. The college’s motto, “A Tradition of Excellence – A Legacy of Caring,” frames its philosophy of providing excellent academic programs in an environment where every student matters and every person counts. For more information about the college, visit pharmacy.mercer.edu