Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

Production and characterization of a malaria transmission blocking vaccine candidate Pvs230D1-EPA for human clinical studies (#216)

David L. Narum 1 , Karine Reiter 1 , Vu Nguyen 1 , Raul Herrera 1 , Richard Shimp, Jr. 1 , Kelly M. Rausch 1 , Deepika Seethamraju 1 , Myriam Arevalo 2 , Martin Burkhardt 1 , Olga Muratova 1 , Lynn E. Lambert 1 , Nada Alani 1 , Jen C.C. Hume 1 , Jenny M. Reimer 3 , Emma K. Barnafo 1 , Sachy Orr-Gonzalez 1 , Daming Zhu 1 , Tarik Ouahes 1 , Brandi Butler 1 , Weili Dai 1 , Holly McClellan 1 , Irfan Zaidi 1 , John Woodford 1 , Socrates Herrera 2 , Puthupparampil V. Scaria 1 , Nicholas J. MacDonald 1 , Gale Smith 4 , Greg M. Glenn 4 , Patrick E. Duffy 1
  1. NIAID, NIH, Bethesda, MD, United States
  2. Caucaseco Scientific Research Center, Cali, Colombia
  3. Novavax AB, Uppsala, Sweden
  4. Novavax, Inc, Gaithersburg, MD

A Plasmodium vivax transmission blocking vaccine could potentially play a critical role in efforts to eliminate and eradicate malaria. We have produced a recombinant form of the P. vivax 230 kDa sexual stage protein comprised of domain 1, similar to Pfs230D1M, following current good manufacturing practices (cGMP), which was then chemically conjugated to ExoProtein A to form a nanoparticle. Pvs230D1M was produced using the Pichia pastoris expression system as a secreted protein and purified using standard column chromatography resins (yield >300 mg/L broth). Pvs230D1M contains no heterologous amino acids or affinity tags. Pvs230D1M and Pvs230D1-EPA have been fully characterized biochemically and biophysically, including (as appropriate) intact mass, N-terminal sequencing, analytical SEC-UPLC with online MALS, reversed-phase-UPLC, and host-cell protein content. The Pvs230D1-EPA conjugated nanoparticle was determined suitable for human clinical trials. Two murine monoclonal antibodies have been generated for Pvs230D1M identification, and one of these demonstrates transmission reducing activity. Rabbits were immunized with monomeric Pvs230D1M formulated in Montanide ISA720, or conjugated Pvs230D1-EPA formulated with Matrix-MTM adjuvant. Antibodies from these animals blocked P. vivax transmission in membrane feeding assays using parasites isolated either from naturally infected individuals in Colombia or from infected Saimiri monkeys, respectively.  Human complement significantly enhanced transmission reducing activity. Matrix-MTM adjuvant improved immunogenicity compared to Alhydrogel® in mice and has an established human safety profile. We plan to test a cGMP Pvs230D1-EPA conjugated experimental vaccine formulated with Matrix-MTM adjuvant in a human trial that incorporates controlled human P. vivax challenge to assess efficacy for blocking parasite transmission to mosquitoes.