# A glycolipid adjuvant to promote dose sparing, accelerate immunization schedules and extend durability of high-level protection with an attenuated, live sporozoite malaria vaccine

> **NIH NIH R44** · SANARIA, INC. · 2022 · $999,306

## Abstract

We propose to further enhance Plasmodium falciparum (Pf) Sporozoite (SPZ)-based vaccines
against malaria that are the only immunogens proven to induce >90% short term (3 weeks) and long
term (at least 14 months) protection against controlled human malaria infection with Plasmodium
falciparum (Pf) in humans. Using a unique glycolipid adjuvant 7DW8-5, the goal is to prolong the
duration of vaccine efficacy (VE) and to increase efficacy in endemic settings. In the mouse model
using P. yoelii (Py) sporozoites (SPZ) we achieved > 80% protection at 16 weeks with 2 dose and 4
dose accelerated regimens of irr PySPZ plus 7DW8-5 adjuvant administered by direct venous
inoculation (DVI) representing a 2-fold enhancement over irr PySPZ without adjuvant. The adjuvant
could be mixed with irr PySPZ. High level (>80%) protection of mice persisted at 16 weeks with irr
PySPZ by DVI, in the presence of 7DW8-5, but not by non-DVI routes. Manufacturing of 7DW8-5
under cGMPs was completed and in a pilot study with P. knowlesi (Pk) SPZ, irr PkSPZ we achieved
50% VE and no improvement with the adjuvant, likely attributable to sub-optimal comparative dose or
dosing regimens, or the short-term infectious challenge design. Due to the excellent demonstrable
safety record of the combined SPZ-adjuvant vaccine in NHPs, and comparable bioactivity on co-
culture human iNKT cells in vitro, we propose further optimization of dosing regimens for durable
immunity in pig-tailed macaques, the natural host for Pk, along with protection studies to assess
adjuvant effects on chemically attenuated (PySPZ-chemoprophylaxis vaccine CVac) and genetically
attenuated (PySPZ-LARC) in mice. Using humanized HISA2/ hCD1d mice possessing functional
human CD8+ T cells and human iNKT cells (cellular targets of 7DW8-5) we will investigate whether a
PfSPZ-7DW8-5 combination immunogen can enhance the human CD8+ T-cell response to PfSPZ.
Adjuvant-associated biomarker discovery studies are also planned in mice. Towards clinical use of
the PfSPZ-7DW8-5 combination vaccine, we will establish stability criteria and formulation
methodologies for 7DW8-5, and further comparability testing of GMP-grade 7DW8-5 for bioactivity in
vitro as a lot release attribute and humanized HISA2/ hCD1d mice in vivo, compile a pre-IND package
in preparation for pre-clinical and clinical evaluation of the safety and efficacy of 7DW8-5-PfSPZ
combinations, and manufacture GMP 7DW8-5 for clinical use. Because studies outlined in this project
will be conducted with clinical grade, well characterized 7DW8-5, a positive outcome in our studies
will place us in a position to rapidly design and conduct formal pre-clinical toxicology and/or
biodistribution studies in compliance with FDA mandates for a speedier path to the clinic. Completion
of this project will mark the first development of an adjuvant for a live eukaryotic parasite vaccine.

## Key facts

- **NIH application ID:** 10483594
- **Project number:** 2R44AI125009-04A1
- **Recipient organization:** SANARIA, INC.
- **Principal Investigator:** Sumana Chakravarty
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $999,306
- **Award type:** 2
- **Project period:** 2016-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483594

## Citation

> US National Institutes of Health, RePORTER application 10483594, A glycolipid adjuvant to promote dose sparing, accelerate immunization schedules and extend durability of high-level protection with an attenuated, live sporozoite malaria vaccine (2R44AI125009-04A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10483594. Licensed CC0.

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