Vaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication and clinical trials have targeted zygote antigen Pfs25 for decades. We reported that a Pfs25 protein-protein conjugate vaccine formulated in alum adjuvant induced significant serum functional activity in both US and Malian adults. However, antibody titers declined rapidly, and transmission-reducing activity required four vaccine doses. Functional immunogenicity and durability must be improved before advancing TBV further in clinical development. We hypothesized that the pre-fertilization protein Pfs230 alone or in combination with Pfs25 would improve functional activity.
Malaria transmission-blocking vaccines (TBVs) aim to inhibit parasite fertilization or further development within the mosquito midgut. Because TBV-immunized individuals reduce the transmission of malaria parasites to mosquito vectors, TBVs could serve as a promising strategy to eliminate malaria.
Transmission-blocking vaccine (TBV) is a promising strategy to interfere with the transmission of malaria. To date, only limited TBV candidate antigens have been identified for Plasmodium vivax. HAP2 is a gamete membrane fusion protein, with homology to the class II viral fusion proteins. Herein we reported the characterization of the PvHAP2 for its potential as a TBV candidate for P. vivax.
The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines. However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus on the C-terminal six cysteine domain (6C) with the use of fusion proteins to facilitate expression and folding. In this study, we utilized the baculovirus system to evaluate the expression of three Pfs48/45 proteins including the full-length protein, the 6C domain fragment and the 6C domain mutant to prevent glycosylation.
Plasmodium falciparum malaria continues to evade control efforts, utilizing highly specialized sexual-stages to transmit infection between the human host and mosquito vector. In a vaccination model, antibodies directed to sexual-stage antigens, when ingested in the mosquito blood meal, can inhibit parasite growth in the midgut and consequently arrest transmission. Despite multiple datasets for the Plasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development.
The scientific community worldwide has realized that malaria elimination will not be possible without development of safe and effective transmission-blocking interventions. Primaquine, the only WHO recommended transmission-blocking drug, is not extensively utilized because of the toxicity issues in G6PD deficient individuals.
Malaria parasites undergo several stages in their complex lifecycle. To achieve reductions in both the individual disease burden and malaria transmission within communities, a multi-stage malaria vaccine with high effectiveness and durability is a more efficacious strategy compared with a single-stage vaccine.