Vaccines against the sexual stages of the malarial parasite Plasmodium falciparum are indispensable for controlling malaria and abrogating the spread of drug-resistant parasites. Pfs25, a surface antigen of the sexual stage of P. falciparum, is a leading candidate for transmission-blocking vaccine development. While clinical trials have reported that Pfs25-based vaccines are safe and effective in inducing transmission-blocking antibodies, the extent of the genetic diversity of Pfs25 in malaria endemic populations has rarely been studied. Thus, this study aimed to investigate the global diversity of Pfs25 in P. falciparum populations.
The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are leading candidates for a malaria transmission-blocking vaccine (TBV). Previously, we showed that a Pfs230-Pfs48/45 fusion protein elicits higher levels of functional antibodies than the individual antigens, but low yields hampered progression to clinical evaluation. Here we identified a modified construct (ProC6C) with a circumsporozoite protein (CSP) repeat-linker sequence that enhances expression.
Malaria vaccines that disrupt the Plasmodium life cycle in mosquitoes and reduce parasite transmission in endemic areas are termed transmission-blocking vaccines (TBVs). Despite decades of research, there are only a few Plasmodium falciparum antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So far, only two TBV candidates have advanced to phase 1/2 clinical testing with limited success.
The development of the anti-malaria vaccine holds a promising future in malaria control. One of the anti-malaria vaccine strategies known as the transmission-blocking vaccine (TBV) is to inhibit the parasite transmission between humans and mosquitoes by targeting the parasite gametocyte. Previously, we found that P48/45 included in the 6-Cysteine protein family shared by Plasmodium sp. We also detected vaccine properties possessed by all human-infecting Plasmodium and could be used as a cross-species anti-malaria vaccine.
Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually.
Malaria transmission-blocking vaccines (TBVs) could help break the cycle of malaria transmission by conferring community rather than individual protection. When introducing new intervention strategies, uptake is dependent on acceptability, not just efficacy. In this exploratory study on acceptability of TBVs in Sierra Leone, it was hypothesized that TBVs would be largely acceptable to adults and health workers in areas with relatively few ongoing malaria interventions, and that (i) knowledge of malaria and vaccines, (ii) health behaviours associated with malaria and vaccines, and (iii) attitudes towards different vaccines types could lead to greater TBV acceptability.
Malaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1.
Transmission-blocking vaccines (TBV) prevent community spread of malaria by targeting mosquito sexual stage parasites, a life-cycle bottleneck, and will be used in elimination programs. TBV rely on herd immunity to reduce mosquito infections and thereby new infections in both vaccine recipients and non-recipients, but do not provide protection once an individual receives an infectious mosquito bite which complicates clinical development.
Plasmodium vivax is the most widespread malaria species parasitizing humans outside Africa, with approximately 100 million cases reported per year. Most human cases of P. vivax are asymptomatic with low parasitemia, making active case detection-based elimination programme challenging and less effective. Despite the widespread distribution of P. vivax, no effective vaccines are currently available. Transmission blocking vaccines have recently emerged as potential vaccine candidates to reduce transmission rates to below the essential levels required for the maintenance of the parasite life cycle.
The development of effective vaccines remains a major health priority to combat the global burden of malaria, a life-threatening disease caused by Plasmodium parasites. Transmission-blocking vaccines (TBVs) elicit antibodies that neutralize the sexual stages of the parasite in blood meals ingested by the Anopheles mosquito, interrupting parasite development in the vector host and preventing disease spread to other individuals.