Sanaria®/Seattle Children’s PfSPZ-LARC2 Vaccine: finalist in Vaccine Industry Excellence (VIE) awards for Best Prophylactic Vaccine Award

PfSPZ-LARC2 parasite in hepatocyte of a human-liver-chimeric mouse, six days after sporozoite injection. Parasite circumsporozoite protein (green) and parasitophorous vacuole membrane Exp1 (red) are seen fragmenting, as mature merozoites, essential for the transition to blood stage infection, fail to develop. Liver and parasite DNA is stained with DAPI (blue). Image courtesy of Dr. D. Goswami and Dr. S. Kappe, Seattle Children’s Research Institute.

To protect against and eliminate Plasmodium falciparum (Pf) malaria, the world needs a vaccine that has >90% vaccine efficacy against infection with naturally transmitted Pf parasites. Pf is responsible for >98% of the annual 625,000 deaths from malaria.

Sanaria’s PfSPZ vaccines are composed of PfSPZ harvested from the salivary glands of aseptically reared mosquitoes, that are then purified, vialed, and cryopreserved.

Each generation of PfSPZ vaccine is attenuated in a different way. The first-generation Sanaria® PfSPZ Vaccine, is radiation-attenuated and has shown 100% vaccine efficacy against controlled human malaria infection with Pf and >60% vaccine efficacy without boosting through two years of intense natural malaria transmission. The vaccine is well tolerated and safe, with no differences in safety signals between recipients of vaccine and normal saline placebo controls.

Sanaria’s second-generation vaccine, Sanaria® PfSPZ-CVac (CQ) is chemo-attenuated, composed of infectious PfSPZ co-administered with chloroquine (CQ). At a dose 4.5-fold lower than with PfSPZ Vaccine, PfSPZ-CVac (CQ) conferred 100% cross-strain protection at 12 weeks, which has never been achieved by PfSPZ Vaccine. While this is the best vaccine efficacy ever documented against malaria, production of blood stage parasites leads to malaria symptoms and the risk of a dangerous blood stage infection if the CQ levels in the plasma are inadequate. This creates potential safety and tolerability issues that preclude further development of PfSPZ-CVac (CQ).

The extraordinary safety of PfSPZ Vaccine and the extraordinary efficacy of PfSPZ-CVac (CQ) are now combined in Sanaria/Seattle Children’s third-generation vaccine, Sanaria®PfSPZ-LARC2 Vaccine, developed in collaboration with with the Kappe lab at Seattle Children’s Research Institute (SCRI). The SCRI team carefully selected two genes and deleted them from the parasite genome. Each gene is critical for the developmental transition of the parasite from a benign liver stage infection to a dangerous blood stage infection, both were deleted to ensure complete attenuation and safety. The parasite is thus “late liver-stage arresting, replication competent” (LARC), designed to induce a strong, protective immunity in the liver. In the Netherlands, a PfSPZ-LARC parasite with one of the two genes deleted and administered by mosquito bite rather than injection gave >90% vaccine efficacy against CHMI.

PfSPZ-LARC2 Vaccine, an elegantly designed, genetically attenuated whole parasite vaccine is the result of nearly 20 years of laboratory and clinical work. This vaccine has the potential to save millions of lives and eliminate malaria from defined geographic areas when administered in mass vaccination programs. PfSPZ-LARC2 Vaccine will be assessed in clinical trials in 2024 in the US, Germany, and Burkina Faso.

The 17th Annual ViE Awards 2024, part of the World Vaccine Congress Washington, will celebrate the industry’s most outstanding achievements. With 13 categories, these awards have been created to honor and generate recognition of the efforts, accomplishments, and positive contributions of companies and individuals in the vaccine industry. Sanaria is grateful for PfSPZ-LARC2 Vaccine being recognized as a finalist in this year’s nominations for “Best Prophylactic Vaccine Award” alongside GSK, Pfizer, Sanofi, Takeda and Valneva.