# In-Vitro Culture of Plasmodium falciparum Sporozoites for Malaria Vaccine

> **NIH NIH R44** · SANARIA, INC. · 2022 · $947,054

## Abstract

Abstract
The WHO estimates that in 2017, malaria caused 219M clinical episodes and 435,000 deaths worldwide. 2017
was the 3rd consecutive year in which there was no decrease, instead an increase in malaria morbidity and
mortality worldwide. A vaccine would the most efficient, cost-effective way to control malaria, yet despite
billions of dollars of investment, there is no malaria vaccine with market authorization (licensure) by any
regulatory body in the world. Sanaria’s platform technology, aseptic, purified, cryopreserved Plasmodium
falciparum (Pf) sporozoites (SPZ), has enabled the development of the world’s most protective malaria
vaccines. These PfSPZ-based vaccines have been assessed in 9 countries, 6 in Africa. PfSPZ Vaccine
(radiation-attenuated) is extremely safe and well-tolerated and has induced >90% vaccine efficacy (VE)
against homologous (same strains of Pf in vaccine and challenge) controlled human malaria (CHMI) at 3-11
weeks after immunization in the US, Germany, Mali and Tanzania; 80% and 54% VE against heterologous
(different strains of Pf in vaccine and challenge) CHMI at 2.5 and 8 months; and ~50% VE for 6 months against
intense naturally transmitted Pf malaria in 3 field trials in Africa. It is now advancing to Phase 3 clinical trials
and licensure. Sanaria’s second generation vaccine, PfSPZ-CVac (chemo-attenuated) is more protective than
PfSPZ Vaccine, and genetically-attenuated PfSPZ will follow. Long-term success will require improved
products and more efficient, less costly manufacturing to decrease cost-of-goods (COGs). This Phase II SBIR
competitive renewal supports the latter by eliminating aseptic mosquitoes from the manufacturing process
through in vitro production of PfSPZ (iPfSPZ). In and subsequent to our successful Phase II SBIR, we 1)
introduced a hollow fiber bioreactor (HFB) for producing iPfSPZ at scale, producing “billions” of motile, PfSPZ-
expressing PfCSP, with a conversion from gametocytes to Pf sporozoites ~30-times higher in vitro compared
to in mosquitoes. GMP compliant materials were used throughout and we partially purified iPfSPZ; 2)
demonstrated that the iPfSPZ were infectious to hepatocytes in vitro and to mice with human livers and human
erythrocytes in vivo (a first in the history of malaria biology), and that despite being able to fully develop in
human livers to infect human erythrocytes, the iPfSPZ may be intrinsically, partially attenuated at the late liver
stage. In this Phase II project, we will demonstrate immunogenicity and protective efficacy of iPfSPZ in Aotus
monkeys; further refine, optimize, and scale-up production and purification of potent iPfSPZ; optimize the
cryopreservation process of iPfSPZs; develop, establish and conduct a quality control (QC) purity assay for
product release; and manufacture a lot of aseptic, purified, cryopreserved iPfSPZ that meets QC release assay
specifications for use in IND-directed studies. Switching to in vitro production of iPfSPZ, thereby elimin...

## Key facts

- **NIH application ID:** 10408781
- **Project number:** 5R44AI085740-08
- **Recipient organization:** SANARIA, INC.
- **Principal Investigator:** STEPHEN Lev HOFFMAN
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $947,054
- **Award type:** 5
- **Project period:** 2010-02-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408781

## Citation

> US National Institutes of Health, RePORTER application 10408781, In-Vitro Culture of Plasmodium falciparum Sporozoites for Malaria Vaccine (5R44AI085740-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408781. Licensed CC0.

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