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  - Maiden, Martin C. J.
A1  - Frosch, Matthias
T1  - Can we, should we, eradicate the meningococcus?
JF  - Vaccine
N2  - The eradication of infectious agents is an attractive means of disease control that, to date, has been achieved for only one human pathogen, the smallpox virus. The introduction of vaccines against Neisseria meningitidis into immunisation schedules, and particularly the conjugate polysaccharide vaccines which can interrupt transmission, raises the question of whether disease caused by this obligate human bacterium can be controlled, eliminated, or even eradicated. The limited number of meningococcal serogroups, lack of an animal reservoir, and importance of meningococcal disease are considerations in favour of eradication; however, the commensal nature of most infections, the high diversity of meningococcal populations, and the lack of comprehensive vaccines are all factors that suggest that this is not feasible. Indeed, any such attempt might be harmful by perturbing the human microbiome and its interaction with the immune system. On balance, the control and possible elimination of disease caused by particular disease-associated meningococcal genotypes is a more achievable and worthwhile goal.
KW  - population biology
KW  - epidemiology
KW  - vaccines
KW  - neisseria meningitidis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125646
VL  - 30
IS  - Suppl. 2
ER  -