The National Institutes of Health has awarded a research program project grant to Mary Klotman, MD, professor of medicine (Infectious Diseases). The award will last five years, and will total more than $9 million.
The program project, Integrase Defective Lentiviral Vector (IDLV)-ENV Immunogen Strategy for an HIV Vaccine, is supported by the National Institute Of Allergy and Infectious Diseases under award number P01AI110485.
“This grant represents an exciting collaborative effort,” said Klotman. “It combines our long-standing interest in developing integrase defective lentiviral vectors as a safe approach to persistent immunogen expression along with expertise within the Duke Human Vaccine Institute on innovative envelope immunogen design and comprehensive vaccine assessment."
The award will support two research projects and two core facilities. Overall, the program project will test the hypothesis that delivery of HIV antigens in IDLV results in safe and sustained in vivo expression that drives mature, durable and effective T cell and B cell responses. The goal is a safe, effective HIV vaccine.
The first project, Safety and Durability of Integrase Defective Lentiviral vector for an HIV Vaccine, is directed by Klotman and Andrea Cara, PhD, a Duke visiting scholar. Klotman and Cara have collaborated and published jointly for more than 12 years on IDLV development.
The second project, Antibody Maturation Elicited by Integrase Defective Lentiviral Vectors, is directed by Michael Anthony Moody, MD, associate professor of pediatrics (Infectious Diseases) and director of the Laboratory of B cell Immunotechnology in the Duke Human Vaccine Institute.
The NHP (non human primate) Core for Development of an Integrase Defective Lentiviral Vector HIV Vaccine will be lead by Sampa Santra, PhD, assistant professor of medicine at Harvard University and a member of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center.
Klotman's lab includes Dr. Cara; Bala Balakumaran, PhD; Maria Blasi, PhD; Donatella Negri, PhD; and Emily Camp, a PhD student.
“I am very excited to be part of this project,” said Dr. Cara. “We have been working for a long time on a delivery system with high immunogenicity profile and low anti-vector immune response, and we hope that IDLV will do the trick.”
Among many important contributions to this field, Klotman and her team demonstrated that HIV resides in and evolves separately in kidney cells, a critical step in HIV-associated kidney disease.
Her research group also has determined the role of soluble host factors involved in an innate immune response to HIV in an effort to improve prevention strategies, topical microbicides that could be used to block sexual transmission of HIV.