Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
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Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.
Lancet Infect Dis
December 2024
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:
Background: Plasmodium falciparum parasitaemia during pregnancy causes maternal, fetal, and infant mortality. Poor pregnancy outcomes are related to blood-stage parasite sequestration and the ensuing inflammatory response in the placenta, which decreases over successive pregnancies. A radiation-attenuated, non-replicating, whole-organism vaccine based on P falciparum sporozoites (PfSPZ Vaccine) has shown efficacy at preventing infection in African adults.
View Article and Find Full Text PDFImplementation of a Randomized, Placebo-Controlled Trial of Live Attenuated Malaria Sporozoite Vaccines in an Indonesian Military Study Population.
Am J Trop Med Hyg
May 2024
Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Malaria eradication efforts prioritize safe and efficient vaccination strategies, although none with high-level efficacy against malaria infection are yet available. Among several vaccine candidates, Sanaria® PfSPZ Vaccine and Sanaria PfSPZ-CVac are, respectively, live radiation- and chemo-attenuated sporozoite vaccines designed to prevent infection with Plasmodium falciparum, the leading cause of malaria-related morbidity and mortality. We are conducting a randomized normal saline placebo-controlled trial called IDSPZV1 that will analyze the safety, tolerability, immunogenicity, and efficacy of PfSPZ Vaccine and PfSPZ-CVac administered pre-deployment to malaria-naive Indonesian soldiers assigned to temporary duties in a high malaria transmission area.
View Article and Find Full Text PDFA replication competent Plasmodium falciparum parasite completely attenuated by dual gene deletion.
EMBO Mol Med
April 2024
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
Vaccination with infectious Plasmodium falciparum (Pf) sporozoites (SPZ) administered with antimalarial drugs (PfSPZ-CVac), confers superior sterilizing protection against infection when compared to vaccination with replication-deficient, radiation-attenuated PfSPZ. However, the requirement for drug administration constitutes a major limitation for PfSPZ-CVac. To obviate this limitation, we generated late liver stage-arresting replication competent (LARC) parasites by deletion of the Mei2 and LINUP genes (mei2/linup or LARC2).
View Article and Find Full Text PDFSafety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults.
J Clin Invest
January 2024
Sanaria Inc., Rockville, Maryland, USA.
BACKGROUNDSanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive (HIV+) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown.METHODSThis randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV-) and well-controlled HIV+ Tanzanians (HIV viral load <40 copies/mL, CD4 counts >500 cells/μL).
View Article and Find Full Text PDFSporozoite immunization: innovative translational science to support the fight against malaria.
Expert Rev Vaccines
November 2023
Sanaria Inc, Rockville, MD, USA.
Introduction: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for (Pf), the deadliest human malaria parasite.
Areas Covered: Sporozoites (SPZ), the parasite stage transmitted by mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection.
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