The Inaugural Richard J. Meyer Endowed Lecture, featuring Dr. Simon J. Draper, Professor of Vaccinology and Translational Medicine in the Department of Biochemistry, University of Oxford, England was recently held Oct. 17, 2023. The title of Dr. Draper’s lecture was Advances in Vaccines and Antibodies for Blood-Stage Human Malaria.
Dr. Ian Molineux, LCID Faculty member and Professor of Molecular Biosciences, made opening remarks prior to Dr. Draper’s lecture. He spoke about Dr. Meyer’s research and his legacy. Dr. Meyer came to the University in January of 1978 as a member of the Department of Microbiology and later the merged Molecular Genetics and Microbiology Department and the Molecular Biosciences Department. For his entire career Dr. Meyer studied the DNA of bacterial plasmids to understand how they develop antibiotic resistance in hopes of creating ways to limit the spread of this antibiotic resistance. He continued with this work until he retired from UT in 2017. He passed away in 2022.
Draper Discusses Development of Blood-Stage Vaccine for Pf Malaria
Dr. Draper began his lecture talking about the effects of malaria, specifically malaria caused by the parasite Plasmodium falciparum (Pf) in humans, and primarily children, on the African continent. Pf malaria is the deadliest form of malaria affecting humans and is responsible for around 50% of all malaria cases worldwide, with most cases occurring on the African continent. It causes 600,000 deaths a year, particularly in children under 5 years old in sub-Saharan Africa.
Draper explained that Pf malaria is caused by the bite of a female mosquito that releases parasites called sporozoites that go into the skin and then migrate rapidly to the liver where they replicate and form merozoites that are released into the bloodstream that then infect red blood cells. It’s this blood stage of infection that leads to the clinical symptoms and associated morbidity and mortality from malaria.
The disease had been in decline since the beginning of the millennium as a result of preventative measures such as spraying of mosquitos and insecticide treated bed netting as well as anti-malarial drugs. However, Draper said that since 2015 the disease has been on the rise.
To address this increase in malaria cases, anti-circumsporozoite protein (CSP) vaccines that target sporozoites were developed and recently approved by the World Health Organization (WHO). These vaccines have been trialed and used in the last couple of years in African countries, and while successful, they have moderate efficacy at their peak and the antibodies wane over time. Scientists, including Draper and his team at the University of Oxford, have been researching a complementary vaccine that makes a second level of defense at the blood stage level that could improve durability of protection over use of the anti-CSP vaccines alone.
By looking at the immuno-biology of the merozoite, Draper and his team, along with other labs, were able to identify vulnerabilities that enabled the Draper team to develop blood-stage vaccines to target these vulnerabilities as well as create a high level of antibody to stop the infection since the parasite moves so quickly. These vaccines have all showed promising results in both animal and human trials, enabling them to achieve a threshold of antibody levels and durability that previous vaccines could not do. This is particularly compelling in clinical studies of African infants, who suffer the most from Pf malaria.
They also discovered that increasing the number of months between the first vaccine and the booster and lowering the dose has shown durability of vaccine antibodies for up to 2 years in vaccinated adults. This particular study was done in collaboration with the UT Austin team of LCID Faculty member Greg Ippolito, Chemical Engineering Research Assistant Jason Lavinder and Biomedical Engineering Graduate Fellow Jeffrey Marchioni. Follow up studies done in African infants are now in progress.
Second-generation blood-stage vaccines have also now been developed and are being studied. Draper hopes to have the first clinical efficacy data on these vaccines from Phase 1 and 2 trials during 2024.
Studies in other labs have also shed more light into the biology of the blood-stage merozoite and found other vulnerabilities which have been helpful in further vaccine development. Draper and his team, working with collaborators, have also continued to study the structures of the antibodies created by their current blood-stage vaccines to see how they stop or slow down infection. This has led to the development of a monoclonal antibody-based biologic that in humanized mouse studies shows high levels of protection which look promising for future trials in humans.
All in all, the future of blood-stage malaria vaccines to complement anti-CSP vaccines looks highly promising. Draper said, “We hope these will lead to higher and more durable efficacy against Pf malaria.”
About the Richard J. Meyer Endowment
The endowment for the Richard J. Meyer Endowed Lecture was established by LCID Director Shelley Payne and LCID Associate Director Jaquelin Dudley in memory of their friend and colleague. This endowment recognizes Dr. Meyer’s contributions to science and his training of Microbiology graduate students. The lectureship supports an annual lecture through the LaMontagne Center for Infectious Diseases to allow LCID faculty, students, and postdoctoral fellows to learn cutting edge information that will inspire their research. To donate to the endowment, please go to https://cid.utexas.edu/funding-initiatives.