Safety, immunogencity, and efficacy of PfSPZ LARC2 malaria vaccine in malaria-exposed adults and children - PROJECT SUMMARY/ABSTRACT
Malaria cases and deaths have been unchanged for the past 6 years despite $3-4 B annual investment in control
measures. A highly efficacious vaccine would save lives by providing durable protection against infection and
support global eradication efforts by blocking transmission. Current malaria control strategies including
insecticide-impregnated bed nets, indoor residual spraying and antimalarial drugs have reduced malaria rates in
many countries, but malaria still causes 247 million cases and 619,000 deaths annually. In late 2022, the WHO
published its Preferred Product Characteristics for Malaria Vaccines. Strategic Goal 1 was, “Malaria vaccines
that prevent human blood-stage infection at the individual level in >90% of recipients.” Successful development
and deployment of a highly efficacious malaria vaccine with these characteristics would both reduce malaria
morbidity and mortality and accelerate malaria eradication efforts. The only malaria vaccines that have ever
reached this level of efficacy have been Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines, including PfSPZ
Vaccine and PfSPZ-CVac. To achieve the tolerability and safety of PfSPZ Vaccine and the VE and potency of
PfSPZ-CVac, a 3rd generation vaccine has been created and manufactured in compliance with cGMPs. PfSPZ-
LARC2 is a late arresting replication competent (LARC) parasite, attenuated by deletion of two genes. PfSPZ-
LARC2 Vaccine will undergo clinical assessment of tolerability, safety, and vaccine efficacy (VE) in 2023 in the
US and Germany. The next steps for clinical development of PfSPZ-LARC2 Vaccine include safety and
immunogenicity testing in malaria-experienced adults with subsequent age de-escalation and additional safety,
immunogenicity, and VE testing in children living in a highly endemic area. The proposed research seeks to plan
for a two-part clinical trial in a highly endemic area of Burkina Faso. Part one will include testing in adults,
adolescents, and children, and part two will expand PfSPZ-LARC2 Vaccine testing in children. Planning activities
that will be supported by the current proposal include development of the clinical trial protocol, informed consent
form, manual of procedures, case report forms, data management plan, data and safety monitoring plan,
protocol-specific training materials and plans for study staff, trial budget, study product management plan, and
regulatory submission plan.
