Distinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1

Yi Cao; Maisa da Silva Araujo; Cynthia G Lorang; Najara Akira Costa Dos Santos; Abhai Tripathi; Joseph Vinetz; Nirbhay Kumar

doi:10.1016/j.vaccine.2024.126696

Distinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1

Vaccine. 2025 Jan 8:47:126696. doi: 10.1016/j.vaccine.2024.126696. Online ahead of print.

Authors

Yi Cao¹, Maisa da Silva Araujo², Cynthia G Lorang¹, Najara Akira Costa Dos Santos³, Abhai Tripathi⁴, Joseph Vinetz⁵, Nirbhay Kumar⁶

Affiliations

¹ Department of Global Health, George Washington University, Washington, D.C., USA.
² Plataforma de Produção e Infecção de Vetores da Malária, Laboratório de Entomologia - FIOCRUZ RO, Rua da Beira 7671, CEP 76812-245 Porto Velho, RO, Brazil; Laboratório de Pesquisa Translacional e Clínica, Centro de Pesquisa em Medicina Tropical, Porto Velho, Rondônia, Brazil.
³ Plataforma de Produção e Infecção de Vetores da Malária, Laboratório de Entomologia - FIOCRUZ RO, Rua da Beira 7671, CEP 76812-245 Porto Velho, RO, Brazil.
⁴ Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁵ Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
⁶ Department of Global Health, George Washington University, Washington, D.C., USA. Electronic address: nkumar@gwu.edu.

PMID: 39787798
DOI: 10.1016/j.vaccine.2024.126696

Abstract

Transmission-blocking vaccines (TBVs) targeting sexual-stage antigens represent a critical tool for malaria control and elimination through inhibiting parasite development within mosquitoes. P230, displayed on the surface of gametocytes and gametes, plays a crucial role in gamete fertilization and is one of the leading TBV candidates for both Plasmodium falciparum and P. vivax. Antibodies induced by immunization with a recombinant P. falciparum protein encompassing a portion of N-terminal prodomain and domain 1 (Pfs230D1M) have revealed strong transmission-reducing activity (TRA) in preclinical studies. While a recombinant Pvs230D1, the P. vivax homolog of Pfs230D1M, has not been evaluated in preclinical immunogenicity studies, both Pfs230D1M and Pvs230D1 are currently scheduled for evaluation in clinical trials. In this study, we developed DNA vaccines encoding Pfs230D1M and Pvs230D1 for a side-by-side comparison of their immunogenicity. Potent antibody responses were induced in mice immunized with each DNA vaccine delivered by in vivo electroporation (EP). Anti-Pfs230D1M IgG exhibited potent dose-dependent TRA in a complement-dependent manner in standard membrane feeding assays (SMFA). In contrast, anti-Pvs230D1 IgG exhibited only moderate TRA in direct membrane feeding assay (DMFA) using blood from multiple P. vivax-infected donors. Antibodies induced by the Pfs230D1M DNA vaccine revealed a strong IgG1 bias and higher avidity as compared to a balanced IgG1/IgG2 response and lower antibody avidity by the Pvs230D1 DNA vaccine. Our results demonstrate the potential of both Pfs230D1M and Pvs230D1 DNA vaccines as TBV candidates against P. falciparum and P. vivax, and provide a rationale for future optimization to enhance the efficacy of DNA vaccines based on Pfs230 and Pvs230.

Keywords: DNA vaccines; P230D1; Plasmodium falciparum; Plasmodium vivax; Transmission-blocking antigens.