Browsing by Author "Roeffen, W."
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Item A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages(Elsevier BV, 2014) Theisen, M.; Roeffen, W.; Singh, S.K.; Andersen, G.; Amoah, L.; van de Vegte-Bolmer, M.; Arens, T.; Jones, S.; Bousema, T.; Adu, B.; Dziegiel, M.H.; Christiansen, M.; Sauerwein, R.Effective control and eventual eradication of malaria drives the imperative need for clinical development of a malaria vaccine. Asexual parasite forms are responsible for clinical disease and death while apathogenic gametocytes are responsible for transmission from man to mosquito. Vaccines that combine antigens from both stages may provide direct protection and indirect benefit by reducing the force of infection. We constructed a chimeric antigen composed of a fragment of the Plasmodium falciparum (Pf) glutamate-rich protein fused in frame to a correctly folded fragment of Pfs48/45. The chimera was produced in Lactococcus lactis and induced robust antibody responses in rodents to the individual components. Specific antibodies showed strong transmission blocking activity against multiple Pf-strains in the standard membrane feeding assay and functional activity against asexual stages in the antibody dependent cellular inhibition assay. The combined data provide a strong rationale for entering the next phase of clinical grade production and testing. © 2014 Elsevier Ltd.Item Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates(Journal of Infection, 2015-07) Jones, S.; Grignard, L.; Nebie, I.; Chilongola, J.; Dodoo, D.; Sauerwein, R.; Theisen, M.; Roeffen, W.; Singh, S.K.; Singh, R.K.; Singh, S.; Kyei-Baafour, E.; Tetteh, K.; Drakeley, C.; Bousema, T.Objectives: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. Methods: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. Results: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p<0.001) and 230CMB (p=0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p=0.017) and 230CMB (p=0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. Conclusions: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. © 2015 The British Infection Association.