Patrick E. Duffy, M.D.

The Vaccine Development Unit (VDU) conceives, produces, and tests novel malaria vaccine approaches. Since LMIV was launched in 2009, the team has emphasized malaria eradication as a vaccine goal, using a so-called vaccine to interrupt malaria transmission (VIMT). VIMT can include transmission-blocking, pre-erythrocytic, and potentially other components. In addition, VDU pursues concepts to protect pregnant women and their infants.

Transmission-Blocking Vaccines (TBV)

TBVs are unlike other malaria vaccine candidates: they do not protect recipients from infection or disease, and instead prevent infection of mosquitoes to reduce malaria in a community. LMIV has the world’s leading TBV candidate, named Pfs230D1, which induces antibodies that lyse parasites in the mosquito midgut. Pfs230D1 is currently in phase 2 clinical evaluation of safety and functional activity in Mali. We are also conducting clinical trials of TBVs throughout West Africa, in collaboration with partners from the Netherlands, Denmark, Mali, Burkina Faso, Liberia, and Guinea, to build on our success with Pfs230D1.

Pre-Erythrocytic Vaccines (PEV)

Pre-erythrocytic stage vaccines target sporozoite and liver stages that occur just after mosquitoes inject parasites (and just before disease-causing blood stage parasites develop). The GSK vaccine RTS,S is based on the sporozoite surface protein called CSP, and was approved by WHO in 2021 to reduce clinical malaria in young children. To improve on RTS,S vaccine, LMIV and partners have identified novel pre-erythrocytic antigens that enhance protection conferred by CSP in animal models, and are now producing these antigens suitable for testing in human studies.

LMIV works with local biotech Sanaria, Inc. to develop whole sporozoite vaccines. Sanaria manufactures sporozoites (called PfSPZ) suitable for human injection. LMIV and Mali colleagues conducted the first trials showing that Sanaria PfSPZ Vaccine (comprised of irradiated PfSPZ) protects adults from naturally occurring malaria. LMIV also assessed another approach—called “chemoprophylaxis vaccination”, in which live PfSPZ are inoculated while individuals receive antimalarial drugs. Phase 1 studies of this approach, called PfSPZ-CVac, achieved unprecedented durable sterile immunity in US volunteers. LMIV and partners are now conducting clinical field trials of PfSPZ-CVac, and seeking to understand the immunologic mechanism for PfSPZ-CVac potency.

Placental Malaria Vaccines

Placental malaria kills ~50,000 African mothers each year. Malaria-infected erythrocytes use the VAR2CSA surface antigen to bind chondroitin sulfate A (CSA) and sequester in the placenta, with dire sequelae for mothers and offspring. LMIV scientists have gleaned fundamental insights into VAR2CSA biology in recent years and are now developing novel VAR2CSA vaccine designs. LMIV recently reported a nonhuman primate model that recapitulates the features of malaria in pregnant women and is suitable for preclinical testing of VAR2CSA vaccine candidates.

In collaboration with Sanaria, Inc. and Mali colleagues, LMIV is preparing for the first trials of malaria vaccines in pregnant women. LMIV and Mali scientists have completed a trial of Sanaria’s PfSPZ Vaccine that vaccinated women before conception and examined its protective benefits during subsequent pregnancies. Future trials are under design that will assess PfSPZ Vaccine administered during pregnancy.