TY  - JOUR
A1  - Boes, Alexander
A1  - Spiegel, Holger
A1  - Voepel, Nadja
A1  - Edgue, Gueven
A1  - Beiss, Veronique
A1  - Kapelski, Stephanie
A1  - Fendel, Rolf
A1  - Scheuermayer, Matthias
A1  - Pradel, Gabriele
A1  - Bolscher, Judith M.
A1  - Behet, Marije C.
A1  - Dechering, Koen J.
A1  - Hermsen, Cornelus C.
A1  - Sauerwein, Robert W.
A1  - Schillberg, Stefan
A1  - Reimann, Andreas
A1  - Fischer, Rainer
T1  - Analysis of a multi-component multi-stage malaria vaccine candidate—tackling the cocktail challenge
JF  - PLoS ONE
N2  - Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17–25 μg/ml), the blood stage (40–60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.
KW  - malaria
KW  - vaccines
KW  - antibodies
KW  - P. falciparum
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173092
VL  - 10
IS  - 7
ER  - 
TY  - JOUR
A1  - Feller, Tatjana
A1  - Thom, Pascal
A1  - Koch, Natalie
A1  - Spiegel, Holger
A1  - Addai-Mensah, Otchere
A1  - Fischer, Rainer
A1  - Reimann, Andreas
A1  - Pradel, Gabriele
A1  - Fendel, Rolf
A1  - Schillberg, Stefan
A1  - Scheuermayer, Matthias
A1  - Schinkel, Helga
T1  - Plant-Based Production of Recombinant Plasmodium Surface Protein Pf38 and Evaluation of its Potential as a Vaccine Candidate
JF  - PLOS ONE
N2  - Pf38 is a surface protein of the malarial parasite Plasmodium falciparum. In this study, we produced and purified recombinant Pf38 and a fusion protein composed of red fluorescent protein and Pf38 (RFP-Pf38) using a transient expression system in the plant Nicotiana benthamiana. To our knowledge, this is the first description of the production of recombinant Pf38. To verify the quality of the recombinant Pf38, plasma from semi-immune African donors was used to confirm specific binding to Pf38. ELISA measurements revealed that immune responses to Pf38 in this African subset were comparable to reactivities to AMA-1 and \(MSP1_{19}\). Pf38 and RFP-Pf38 were successfully used to immunise mice, although titres from these mice were low (on average 1:11.000 and 1:39.000, respectively). In immune fluorescence assays, the purified IgG fraction from the sera of immunised mice recognised Pf38 on the surface of schizonts, gametocytes, macrogametes and zygotes, but not sporozoites. Growth inhibition assays using \(\alpha Pf38\) antibodies demonstrated strong inhibition \((\geq 60 \% ) \) of the growth of blood-stage P. falciparum. The development of zygotes was also effectively inhibited by \(\alpha Pf38\) antibodies, as determined by the zygote development assay. Collectively, these results suggest that Pf38 is an interesting candidate for the development of a malaria vaccine.
KW  - malaria vaccine
KW  - balancing selection
KW  - N-glycans
KW  - falciparum
KW  - expression
KW  - antibodies
KW  - identification
KW  - transmission
KW  - tobacco
KW  - antigen
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128221
SN  - 1932-6203
VL  - 8
IS  - 11
ER  -