Transmission-Blocking Vaccines: Old Friends and New Prospects

Abstract

In the progression of the life cycle of Plasmodium falciparum, a small proportion of asexual parasites differentiate into male or female sexual forms called gametocytes. Just like their asexual counterparts, gametocytes are contained within the infected host's erythrocytes (RBCs). However, unlike their asexual partners, they do not exit the RBC until they are taken up in a blood meal by a mosquito. In the mosquito midgut, they are stimulated to emerge from the RBC, undergo fertilization, and ultimately produce tens of thousands of sporozoites that are infectious to humans. This transmission cycle can be blocked by antibodies targeting proteins exposed on the parasite surface in the mosquito midgut, a process that has led to the development of candidate transmission-blocking vaccines (TBV), including some that are in clinical trials. Here we review the leading TBV antigens and highlight the ongoing search for additional gametocyte/gamete surface antigens, as well as antigens on the surfaces of gametocyte-infected erythrocytes, which can potentially become a new group of TBV candidates.

Diversity and immune responses against Plasmodium falciparum gametocytes in non-febrile school children living in Southern Ghana

“…Antibodies against some gametocyte antigens, including Pfs230 and Pfs48/45 have been shown to reduce malaria transmission due to their possession of transmission reducing activities [13]. Seasonal variations in the prevalence and diversity of gametocytes have the potential to influence malaria transmission as well as the quality and quantity of naturally induced antibodies against these gametocytes in the human hosts.…”

Plasmodium vivax HAP2/GCS1 gene exhibits limited genetic diversity among parasite isolates from the Greater Mekong Subregion

“…Thus, new and integrated intervention strategies to reduce malaria transmission are needed. Among them, transmission-blocking vaccines (TBVs) are considered an integral component of the measures for malaria control and elimination [8][9][10][11].…”

Antibody response of a particle-inducing, liposome vaccine adjuvant admixed with a Pfs230 fragment

“…Malaria is caused by Plasmodium parasites and is transmitted to and from humans by female Anopheles mosquitoes. Transmissionblocking vaccines (TBVs), which block the transmission of parasites to human hosts, have been proposed as a strategy to mitigate disease spread [1][2][3] . TBVs aim to prevent transmission of parasites to other humans following a mosquito blood meal from an infected but TBV-immunized human.…”