In vitro production of infectious Plasmodium falciparum sporozoites.
Abraham G EappenTao LiMeghan MarquetteSumana ChakravartyNatasha KcGigliola ZanghiBenjamin U HoffmanHashani HettiarachchiAsha PatilYonas AbebeChristiane TranAlemtaye A YossefIan McWilliamsRobert D MorrisonAyyappan RathakrishnanEhud InbarAhmed S I AlyPatricia De La VegaMaria BelmonteMartha SedegahTint WaiJoseph J CampoHarley KingStefan H I KappeMingLin LiPeter F BillingsleyB Kim Lee SimStephen L HoffmanPublished in: Nature (2022)
An effective vaccine is needed for the prevention and elimination of malaria. The only immunogens that have been shown to have a protective efficacy of more than 90% against human malaria are Plasmodium falciparum (Pf) sporozoites (PfSPZ) manufactured in mosquitoes (mPfSPZ) 1-7 . The ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research, but this ability is lacking. Here we report the production of hundreds of millions of iPfSPZ. iPfSPZ invaded human hepatocytes in culture and developed to mature liver-stage schizonts expressing P. falciparum merozoite surface protein 1 (PfMSP1) in numbers comparable to mPfSPZ. When injected into FRGhuHep mice containing humanized livers, iPfSPZ invaded the human hepatocytes and developed to PfMSP1-expressing late liver stage parasites at 45% the quantity of cryopreserved mPfSPZ. Human blood from FRGhuHep mice infected with iPfSPZ produced asexual and sexual erythrocytic-stage parasites in culture, and gametocytes developed to PfSPZ when fed to mosquitoes, completing the P. falciparum life cycle from infectious gametocyte to infectious gametocyte without mosquitoes or primates.