Oral presentation | Open | Published:
Viral vectored transmission blocking vaccines against Plasmodium falciparum
Malaria Journalvolume 9, Article number: O22 (2010)
Transmission blocking vaccines (TBVs) target sexual developÂ¬ment of the parasite within the mosquito and aim to prevent transmission of malaria from one individual to another. Antibodies raised against Pfs48/45, Pfs230 Region C, PfHAP2, and Anopheles gambiae Alanyl Aminopeptidase N1 (AgAPN1) proteins reduce transmission i.e. have transmission blocking activity [1–5]. Recombinant simian Adenovirus (AdC63 serotype) and Modified Vaccinia Ankara (MVA) viral vectors have been shown to induce high antibody titres to asexual parasite antigens in animal studies .
Materials and methods
Protein sequences for each of the antigens were codon optimised for expression in humans and cloned into shuttle vectors, which were then recombined with the parental virus and purified to obtain virus expressing the antigen of interest. Mice were vaccinated with AdC63 (i.m.), sera was taken after 2 weeks, and will be followed by an MVA boost (i.d.) eight weeks after the prime. Antibodies were assayed by a standardised ELISA, and transmission blocking activity assessed using a standardised membrane feeding assay (SMFA).
Induction of high antibody tires using this vaccine platform could be used together with other control measures to achieve elimination and/or eradication of the disease at a local or national level.
Dinglasan RR, Kalume DE, Kanzok SM, Ghosh AK, Muratova O, Pandey A, Jacobs-Lorena M: Disruption of Plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen. Proc Natl Acad Sci USA. 2007, 104: 13461-6. 10.1073/pnas.0702239104.
Chowdhury DR, Angov E, Kariuki T, Kumar N: A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli. PLoS One. 2009, 4: e6352-10.1371/journal.pone.0006352.
Bustamante PJ, Woodruff DC, Oh J, Keister DB, Muratova O, Williamson KC: Differential ability of specific regions of Plasmodium falciparum sexual-stage antigen, Pfs230, to induce malaria transmission-blocking immunity. Parasite Immunol. 2000, 22: 373-80. 10.1046/j.1365-3024.2000.00315.x.
Blagborough AM, Sinden RE: Plasmodium berghei HAP2 induces strong malaria transmission-blocking immunity in vivo and in vitro. Vaccine. 2009, 27: 5187-94. 10.1016/j.vaccine.2009.06.069.
Vermeulen AN, Ponnudurai T, Beckers PJ, Verhave JP, Smits MA, Meuwissen JH: Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito. J Exp Med. 1985, 162: 1460-76. 10.1084/jem.162.5.1460.
Draper SJ, Moore AC, Goodman AL, Long CA, Holder AA, Gilbert SC, Hill F, Hill AV: Effective induction of high-titer antibodies by viral vector vaccines. Nat Med. 2008, 14: 819-821. 10.1038/nm.1850.