Malaria Derived Glycosylphosphatidylinositol Anchor Enhances Anti-Pfs25 Functional Antibodies That Block Malaria Transmission.

Abstract

Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development of vaccines to prevent transmission are still needed. Pfs25, a postfertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidylinositol (GPI) linker, which itself possesses pro-inflammatory properties. In this study, Escherichia coli derived extract (XtractCF+TM) was used in cell free protein synthesis [CFPS] to successfully express >200 mg/L of recombinant Pfs25 with a C-terminal non-natural amino acid (nnAA), namely, p-azidomethyl phenylalanine (pAMF), which possesses a reactive azide group. Thereafter, a unique conjugate vaccine (CV), namely, Pfs25-GPI was generated with dibenzocyclooctyne (DBCO) derivatized glycan core of malaria GPI using a simple but highly efficient copper free click chemistry reaction. In mice immunized with Pfs25 or Pfs25-GPI, the Pfs25-GPI group showed significantly higher titers compared to the Pfs25 group. Moreover, only purified IgGs from Pfs25-GPI group were able to significantly block transmission of parasites to mosquitoes, as judged by a standard membrane feeding assay [SMFA]. To our knowledge, this is the first report of the generation of a CV using Pfs25 and malaria specific GPI where the GPI is shown to enhance the ability of Pfs25 to elicit transmission blocking antibodies.

• Authors: Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole A Long, Jeff Fairman, Kazutoyo Miura
• Journal: Biochemistry (Biochemistry) Vol. 57 Issue 5 Pg. 516-519 (02 06 2018) ISSN: 1520-4995 [Electronic] United States
• PMID: 29323879 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Glycosylphosphatidylinositols
• Malaria Vaccines
• Pfs25 protein, Plasmodium falciparum
• Protozoan Proteins
• Vaccines, Conjugate
• Vaccines, Synthetic

Topics

• Animals
• Antibody Formation
• Glycosylphosphatidylinositols (immunology, therapeutic use)
• Humans
• Immunization
• Malaria
• Malaria Vaccines (immunology, therapeutic use)
• Malaria, Falciparum (immunology, prevention & control, transmission)
• Mice
• Plasmodium falciparum (immunology)
• Protozoan Proteins (immunology, therapeutic use)
• Vaccines, Conjugate (immunology, therapeutic use)
• Vaccines, Synthetic (immunology, therapeutic use)