Identification of Novel Malaria Transmission-Blocking Vaccine Candidates.

Eizo Takashima,Masayuki Morita,Hikaru Nagaoka,Takafumi Tsuboi,Bernard N Kanoi,Mayumi Tachibana

doi:10.3389/fcimb.2021.805482

Abstract

Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.

Highlights

Malaria continues to be responsible for a substantial global health burden, with 409,000 malarial deaths reported in 2019 (WHO, 2020)
The principle of malaria transmissionblocking vaccine (TBV) is that antibodies against antigen(s) expressed on the sexual stages of the malaria parasite gametocyte/gamete/zygote/ookinete - reduce the numbers of oocysts in mosquito vectors when fed with gametocytes (Huff et al, 1958; Carter and Chen, 1976; Gwadz, 1976)
Antibodies raised against individual antigens needed to be tested in an ex vivo efficacy assay; the standard membrane feeding assay (SMFA) wherein laboratory-reared Anopheles mosquitoes are fed on in vitro cultured P. falciparum gametocytes along with test antisera or purified antibodies, and counts of midgut wall oocysts as a measure of the degree of transmission-blocking activity (Miura et al, 2013a)

Summary

INTRODUCTION

Malaria continues to be responsible for a substantial global health burden, with 409,000 malarial deaths reported in 2019 (WHO, 2020). A leading malaria vaccine RTS,S/AS01 was the first malaria vaccine to enter Phase III clinical trials and shows modest efficacy against clinical falciparum malaria (RTS, 2015) with short durability (White et al, 2015). The development of erythrocytic stage vaccines to reduce morbidity and mortality, and transmission-blocking vaccines (TBVs) to reduce parasite transmission from humans to mosquitoes, are required to reach the Roadmap goals. The principle of malaria TBVs is that antibodies against antigen(s) expressed on the sexual stages of the malaria parasite gametocyte/gamete/zygote/ookinete - reduce the numbers of oocysts in mosquito vectors when fed with gametocytes (Huff et al, 1958; Carter and Chen, 1976; Gwadz, 1976). Antibodies raised against individual antigens needed to be tested in an ex vivo efficacy assay; the standard membrane feeding assay (SMFA) wherein laboratory-reared Anopheles mosquitoes are fed on in vitro cultured P. falciparum gametocytes along with test antisera or purified antibodies, and counts of midgut wall oocysts as a measure of the degree of transmission-blocking activity (Miura et al, 2013a)

TBV DEVELOPMENT EFFORTS TO DATE

Bacteria Bacteria WGCFS

RODENT MALARIA MODELS FOR NOVEL TBV CANDIDATE DISCOVERY

NOVEL TBV CANDIDATE DISCOVERY DIRECTLY USING HUMAN MALARIA PARASITES

Findings

KEY MESSAGES TO THE NOVEL TBV CANDIDATE DISCOVERY