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

Autor: Cao Y; Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington D.C., USA., Hayashi CTH; Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington D.C., USA., Araujo MDS; 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., Tripathi AK; Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Andrade AO; 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., Medeiros JF; 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., Vinetz J; 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., Kumar N; Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington D.C., USA. Electronic address: nkumar@gwu.edu.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Aug 30; Vol. 42 (21), pp. 126140. Date of Electronic Publication: 2024 Jul 20.
DOI: 10.1016/j.vaccine.2024.07.041
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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