Expression, immunogenicity, histopathology, and potency of a mosquito-based malaria transmission-blocking recombinant vaccine

D. K. Mathias, J. L. Plieskatt, J. S. Armistead, J. M. Bethony, K. B. Abdul-Majid, A. Mcmillan, E. Angov, M. J. Aryee, B. Zhan, P. Gillespie, B. Keegan, A. R. Jariwala, W. Rezende, M. E. Bottazzi, D. G. Scorpio, P. J. Hotez, R. R. Dinglasan

Research output: Contribution to journalArticlepeer-review

Abstract

Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmissionblocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.

Original languageEnglish (US)
Pages (from-to)1606-1614
Number of pages9
JournalInfection and immunity
Volume80
Issue number4
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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