Vaccines and monoclonal antibodies: new tools for malaria control

Abstract

SUMMARYMalaria remains one of the biggest health problems in the world. While significant reductions in malaria morbidity and mortality had been achieved from 2000 to 2015, the favorable trend has stalled, rather significant increases in malaria cases are seen in multiple areas. In 2022, there were 249 million estimated cases, and 608,000 malaria-related deaths, mostly in infants and children aged under 5 years, globally. Therefore, in addition to the expansion of existing anti-malarial control measures, it is critical to develop new tools, such as vaccines and monoclonal antibodies (mAbs), to fight malaria. In the last 2 years, the first and second malaria vaccines, both targeting Plasmodium falciparum circumsporozoite proteins (PfCSP), have been recommended by the World Health Organization to prevent P. falciparum malaria in children living in moderate to high transmission areas. While the approval of the two malaria vaccines is a considerable milestone in vaccine development, they have much room for improvement in efficacy and durability. In addition to the two approved vaccines, recent clinical trials with mAbs against PfCSP, blood-stage vaccines against P. falciparum or P. vivax, and transmission-blocking vaccine or mAb against P. falciparum have shown promising results. This review summarizes the development of the anti-PfCSP vaccines and mAbs, and recent topics in the blood- and transmission-blocking-stage vaccine candidates and mAbs. We further discuss issues of the current vaccines and the directions for the development of next-generation vaccines.

Keywords: CSP; DBP; Duffy-binding protein; Pfs230; Pfs48/45; Plasmodium falciparum; Plasmodium vivax; R21; RH5; RTS,S; circumsporozoite proteins; malaria; monoclonal antibody; reticulocyte-binding protein homolog 5; vaccine.

Fig 1

Life cycle of Plasmodium falciparum, and known effector mechanisms for vaccine-induced immunity.

Fig 2

Plasmodium falciparum CSP (3D7 strain). Epitopes in the repeat domain are recognized by antibodies that neutralize sporozoite infection in humans, and antigen domains are included in RTS,S and R21 vaccines.

Fig 3

Process of merozoite invasion and PCRCR complex. PTRAMP, thrombospondin-related apical merozoite protein; CSS, cysteine-rich small secreted protein; Ripr, RH5 interacting protein; CyRPA, cysteine-rich protective antigen; RH5, reticulocyte-binding protein homolog 5.

Fig 4

Plasmodium falciparum transmission-blocking vaccine (TBV) candidates. AnAPN1, Anopheline alanyl aminopeptidase N; PfMDV-1, male development gene 1.