Evaluation of combination vaccines targeting transmission of Plasmodium falciparum and P. vivax

Yi Cao, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington D.C., USA.
Clifford T. Hayashi, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington D.C., USA.
Maisa da Araujo, 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; Programa de Pós-Graduação em Saúde Pública, Faculdade de Saúde Pública, Universidade Federal de São Paulo, São Paulo 01246-904, SP, Brazil.
Abhai K. Tripathi, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Alice Oliveira Andrade, 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; Programa de Pós-Graduação em Saúde Pública, Faculdade de Saúde Pública, Universidade Federal de São Paulo, São Paulo 01246-904, SP, Brazil.
Jansen Fernandes Medeiros, 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; Programa de Pós-Graduação em Biologia Experimental, Fundação Universidade Federal de Rondônia, Fiocruz Rondônia 76812-245, Brazil.
Joseph Vinetz, Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Sciences, Faculty of Sciences, and Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
Nirbhay Kumar, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington D.C., USA. Electronic address: nkumar@gwu.edu.

Document Type

Journal Article

Publication Date

7-19-2024

Journal

Vaccine

DOI

10.1016/j.vaccine.2024.07.041

Keywords

Combination DNA vaccines; Malaria; Plasmodium falciparum; Plasmodium vivax; Transmission-blocking antigens

Abstract

Transmission-blocking vaccines interrupting malaria transmission within mosquitoes represent an ideal public health tool to eliminate malaria at the population level. Plasmodium falciparum and P. vivax account for more than 90% of the global malaria burden, co-endemic in many regions of the world. P25 and P48/45 are two leading candidates for both species and have shown promising transmission-blocking activity in preclinical and clinical studies. However, neither of these target antigens as individual vaccines has induced complete transmission inhibition in mosquitoes. In this study, we assessed immunogenicity of combination vaccines based on P25 and P48/45 using a DNA vaccine platform to broaden vaccine specificity against P. falciparum and P. vivax. Individual DNA vaccines encoding Pvs25, Pfs25, Pvs48/45 and Pfs48/45, as well as various combinations including (Pvs25 + Pvs48/45), (Pfs25 + Pfs48/45), (Pvs25 + Pfs25), and (Pvs48/45 + Pfs48/45), were evaluated in mice using in vivo electroporation. Potent antibody responses were induced in mice immunized with individual and combination DNA vaccines, and specific antibody responses were not compromised when combinations of DNA vaccines were evaluated against individual DNA vaccines. The anti-Pvs25 IgG from individual and combination groups revealed concentration-dependent transmission-reducing activity (TRA) in direct membrane feeding assays (DMFA) using blood from P. vivax-infected donors in Brazil and independently in ex vivo MFA using Pvs25-transgenic P. berghei. Similarly, anti-Pfs25 and anti-Pfs48/45 IgGs from mice immunized with Pfs25 and Pfs48/45 DNA vaccines individually and in various combinations revealed antibody dose-dependent TRA in standard membrane feeding assays (SMFA) using culture-derived P. falciparum gametocytes. However, antibodies induced by immunization with Pvs48/45 DNA vaccines were ineffective in DMFA and require further vaccine construct optimization, considering the possibility of induction of both transmission-blocking and transmission-enhancing antibodies revealed by competition ELISA. These studies provide a rationale for combining multiple antigens to simultaneously target transmission of malaria caused by P. falciparum and P. vivax.

Department

Global Health

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