Macaca mulatta monkeys were immunized with the candidate transmission-blocking vaccine against Plasmodium vivax, Pvs25, combined with alum or Montanide ISA 720. Efficacy was measured by combining post-immunization sera with gametocytes obtained from infections induced in chimpanzees using membrane-feeding techniques. The results indicate that immunization of M. mulatta monkeys with Pvs25 and Montanide ISA 720 was more effective than with alum in efficacy and resulted in the maintenance of a lasting transmission-blocking immunity to P. vivax. This was evident two weeks after the second immunization, and more strongly demonstrable 62 and 152 days after the second immunization. This transmission-blocking activity was strongly reinforced by a third immunization given 181 days after the primary immunization, as measured three weeks later by indirect membrane feeding. The use of gametocytes of P. vivax derived from infections induced in chimpanzees can contribute to the selection of appropriate constructs, formulations, and immunization regimens for the development of effective transmission-blocking vaccines.
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Parasit Vectors
December 2024
Department of Biological Sciences, Florida International University, 11200 SW 8th St, Miami, FL, 33199, USA.
Background: Malaria remains a critical disease. Leucinostatins from the fungus Purpureocillium lilacinum inhibited the transmission of Plasmodium falciparum to mosquitoes via contact.
Methods: Here, we modified the leucinostatin B (LB) C-terminus to make derivatives and examined their inhibition against malaria transmission to mosquitoes.
Front Cell Infect Microbiol
December 2024
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States.
Arthropod-borne viruses or arboviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV) pose significant threats to public health. It is imperative to develop novel methods to control these mosquito-borne viral infections. We previously showed that insulin/insulin-like growth factor-1 signaling (IIS)-dependent activation of ERK and JAK-STAT signaling has significant antiviral activity in insects and human cells.
View Article and Find Full Text PDFSci Adv
December 2024
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Cyclic nucleotide-dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent PDEβ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates.
View Article and Find Full Text PDFCommun Biol
November 2024
Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK.
Plasmodium male and female gametocytes are the gatekeepers of human-to-mosquito transmission, therefore essential for propagation of malaria within a population. Whilst dormant in humans, their divergent roles during transmission become apparent soon after mosquito feeding with a rapid transformation into gametes - males forming eight motile sperm-like cells aiming to fertilise a single female gamete. Little is known about how the parasite fuels this abrupt change, and the potential role played by their large and elaborate cristate mitochondrion.
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