"malaria transmission blocking"

BACKGROUND: Ps 48/45, a Plasmodium gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant P. vivax Ps 48/45 protein (r Pvs 48/45) with sera from P. falciparum -exposed African donors. METHODS: r Pvs 48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria - In addition, BALB/c mice were immunized with the r Pvs 48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of P...

Malaria remains a highly prevalent infectious disease worldwide, particularly in tropical and subtropical regions. Effectively controlling of mosquitoes transmitting of Plasmodium spp. is crucial in to control this disease. A promising strategy involves utilizing plant-derived products, such as the Neem tree (Azadirachta indica), known for its secondary metabolites with biological activity against various insect groups of agricultural and public health importance. This study investigated the effects of a nanoformulation prototype Neem on factors linked to the vector competence of Anopheles aquasalis, a malaria vector in Latin America...

We report the draft whole-genome assembly of Microsporidia sp. MB , a symbiotic malaria-transmission-blocking microsporidian isolated from Anopheles arabiensis in Kenya. The whole-genome sequence of Microsporidia sp. MB has a length of 5,908,979 bp, 2,335 contigs, and an average GC content of 31.12%.

Adjuvants are critical components for vaccines, which enhance the strength and longevity of the antibody response and influence the types of immune response. Limited research has been conducted on the immunogenicity and protective efficacy of various adjuvants in malaria transmission-blocking vaccines (TBVs). In this study, we formulated a promising TBV candidate antigen, the P. berghei ookinete surface antigen PSOP25, with different types of adjuvants, including the TLR4 agonist monophosphoryl lipid A (MPLA), the TLR9 agonist cytosine phosphoguanosine oligodeoxynucleotides (CpG ODN 1826) (CpG), a saponin adjuvant QS-21, aluminum hydroxide (Alum), and two combination adjuvants MPLA + QS-21 and QS-21 + CpG...

Two malaria transmission-blocking vaccine (TBV) candidates, R0.6C and ProC6C, have completed preclinical development including the selection of adjuvants, Alhydrogel® with or without the saponin based adjuvant Matrix-M™. Here, we report on the final drug product (formulation) design of R0.6C and ProC6C and evaluate their safety and biochemical stability in preparation for preclinical and clinical pharmacy handling. The point-of-injection stability studies demonstrated that both the R0.6C and ProC6C antigens are stable on Alhydrogel in the presence or absence of Matrix-M for up to 24 h at room temperature...

BACKGROUND: Malaria transmission blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS: The candidates, R0.6C and ProC6C, share the Plasmodium falciparum sexual stage antigen, Pfs48/45 "6C" domain. R0.6C utilizes the Glutamate Rich Protein (GLURP) as a carrier and ProC6C includes a second domain (Pfs230-Pro) and a short 36 amino acids CSP sequence. Healthy adults (n = 125) from a malaria endemic area of Burkina Faso were immunized with three intramuscular injections, four weeks apart, of 30 μg or 100 μg R0...

Gamete surface protein P48/45 has been shown to be important for male gamete fertility and a strong candidate for the development of a malaria transmission-blocking vaccine (TBV). However, TBV development for Plasmodium vivax homolog Pvs48/45 has been slow because of a number of challenges: availability of conformationally suitable recombinant protein; the lack of an in vivo challenge model; and the inability to produce P. vivax gametocytes in culture to test transmission-blocking activity of antibodies. To support ongoing efforts to develop Pvs48/45 as a potential vaccine candidate, we initiated efforts to develop much needed reagents to move the field forward...

Developing a novel class of vaccine is pivotal for eliminating and eradicating malaria. Preceding investigations demonstrated partial blocking activity in malaria transmission against recombinant vaccine PfHAP2-GCS1 and conserved region of the cd loop. The effectiveness of immune response varies with the size and shape of the self-assembly of peptide nanoparticles (SAPNs) displaying antigen, affected by different components in refolding buffers. Plasmodium falciparum Generative Cell Specific 1 (PfGCS1), a promising malaria transmission-blocking vaccine (TBV) candidate, was expressed, purified, and followed by a four-step refolding process to form nanoparticles (PfGCS1-SAPNs)...

Malaria transmission-blocking vaccines (TBV) are designed to inhibit the sexual stage development of the parasite in the mosquito host and can play a significant role in achieving the goal of malaria elimination. Preclinical and clinical studies using protein-protein conjugates of leading TBV antigens Pfs25 and Pfs230 domain 1 (Pfs230D1) have demonstrated the feasibility of TBV. Nevertheless, other promising vaccine platforms for TBV remain underexplored. The recent success of mRNA vaccines revealed the potential of this technology for infectious diseases...

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that block Plasmodium parasite development in the mosquito midgut, thus preventing mosquitoes from becoming infectious. While the Pro-domain and first of fourteen 6-Cysteine domains (Pro-D1) of the Plasmodium gamete surface protein Pfs230 are known targets of transmission-blocking antibodies, no studies to date have discovered other Pfs230 domains that are functional targets. Here, we show that a murine monoclonal antibody (mAb), 18F25.1, targets Pfs230 Domain 7...

Microsporidia MB is a symbiont with a strong malaria transmission-blocking phenotype in Anopheles arabiensis . It spreads in mosquito populations through mother-to-offspring and sexual transmission. The ability of Microsporidia MB to block Plasmodium transmission, together with its ability to spread within Anopheles populations and its avirulence to the host, makes it a very attractive candidate for developing a key strategy to stop malaria transmissions. Here, we report tissue tropism and localization patterns of Microsporidia MB , which are relevant to its transmission...

Malaria, caused by the unicellular Apicomplexan protozoa of the genus Plasmodium, is an infectious disease transmitted via female Anopheles mosquitoes. The sexual stage (gametocytes) of malaria parasites is the key to the transmission of parasites from vertebrate hosts to mosquitoes, representing critical bottleneck of the parasite life cycle. This study has established a systematic computational pipeline to achieve the genome-wide in silico analysis and find 708 novels potentially indispensable genes for gametocyte development, consisting of 644 protein coding genes, 56 ncRNA genes and 8 pseudogenes, with a total of 191 genes in the transmembrane, 29 protein coding genes to be exported proteins, and 58 genes in apicoplast regions...

The successful completion of gamete fertilization is essential for malaria parasite transmission, and this process can be targeted by intervention strategies. In this study, we identified a conserved gene (PBANKA_0813300) in the rodent malaria parasite Plasmodium berghei, which encodes a protein of 54 kDa (designated as Pbs54). Localization studies indicated that Pbs54 is associated with the plasma membranes of gametes and ookinetes. Functional studies by gene disruption showed that the Δpbs54 parasites had no defect in asexual proliferation, gametocyte development, or gametogenesis...

BACKGROUND: The demonstration that the recently discovered Anopheles symbiont Microsporidia MB blocks malaria transmission in Anopheles arabiensis and undergoes vertical and horizontal transmission suggests that it is a promising candidate for the development of a symbiont-based malaria transmission-blocking strategy. The infection prevalence and characteristics of Microsporidia MB in Anopheles gambiae sensu stricto (s.s.), another primary vector species of malaria in Kenya, were investigated...

Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector. Domain 1 (D1) of Pfs230 is a leading TBV candidate and comprises the majority of transmission-reducing activity (TRA) elicited by Pfs230. Here we show that the fusion of Pfs230D1 to a 60-copy multimer of the catalytic domain of dihydrolipoyl acetyltransferase protein (E2p) results in a single-component nanoparticle composed of 60 copies of the fusion protein with high stability, homogeneity, and production yields...

Pfs25 is a leading antigen for a malaria transmission-blocking vaccine and shows moderate transmission-blocking activity and induction of rapidly decreasing antibody titers in clinical trials. A comprehensive definition of all transmission-reducing epitopes of Pfs25 will inform structure-guided design to enhance Pfs25-based vaccines, leading to potent transmission-blocking activity. Here, we compiled a detailed human antibody epitope map comprising epitope binning data and structures of multiple human monoclonal antibodies, including three new crystal structures of Pfs25 in complex with transmission-reducing antibodies from Malian volunteers immunized with Pfs25 conjugated to EPA and adjuvanted with AS01...

Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug's bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets...

BACKGROUND: Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians. METHODS: We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali...

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Malaria transmission-blocking vaccine candidates Pfs25-EPA and Pfs230D1-EPA target sexual stage development of Plasmodium falciparum parasites in the mosquito host, thereby reducing mosquito infectivity. When formulated on Alhydrogel, Pfs25-EPA has demonstrated safety and immunogenicity in a phase 1 field trial, while Pfs230D1-EPA has shown superior activity to Pfs25-EPA in a phase 1 US trial and has entered phase 2 field trials. Development continues to enhance immunogenicity of these candidates toward producing a vaccine to reduce malaria transmission (VRMT) with both pre-erythrocytic ( i...