Characterization of a novel inhibitory human monoclonal antibody directed against Plasmodium falciparum Apical Membrane Antigen 1.

Authors:
Dr Otchere Addai-Mensah
Dr Otchere Addai-Mensah
Kwame Nkrumah University of Science and Technology
Senior Lecturer and Dean of Faculty
Immunology and Malariology
Kumasi, Ashanti | Ghana

Sci Rep 2016 12 21;6:39462. Epub 2016 Dec 21.

Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.

Malaria remains a major challenge to global health causing extensive morbidity and mortality. Yet, there is no efficient vaccine and the immune response remains incompletely understood. Apical Membrane Antigen 1 (AMA1), a leading vaccine candidate, plays a key role during merozoite invasion into erythrocytes by interacting with Rhoptry Neck Protein 2 (RON2). We generated a human anti-AMA1-antibody (humAbAMA1) by EBV-transformation of sorted B-lymphocytes from a Ghanaian donor and subsequent rescue of antibody variable regions. The antibody was expressed in Nicotiana benthamiana and in HEK239-6E, characterized for binding specificity and epitope, and analyzed for its inhibitory effect on Plasmodium falciparum. The generated humAbAMA1 shows an affinity of 106-135 pM. It inhibits the parasite strain 3D7A growth in vitro with an expression system-independent IC-value of 35 μg/ml (95% confidence interval: 33 μg/ml-37 μg/ml), which is three to eight times lower than the IC-values of inhibitory antibodies 4G2 and 1F9. The epitope was mapped to the close proximity of the RON2-peptide binding groove. Competition for binding between the RON2-peptide and humAbAMA1 was confirmed by surface plasmon resonance spectroscopy measurements. The particularly advantageous inhibitory activity of this fully human antibody might provide a basis for future therapeutic applications.

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep39462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175200PMC
December 2016
46 Reads
5.080 Impact Factor

Publication Analysis

Top Keywords

plasmodium falciparum
8
membrane antigen
8
apical membrane
8
donor subsequent
4
subsequent rescue
4
binding groove
4
b-lymphocytes ghanaian
4
groove competition
4
rescue antibody
4
ghanaian donor
4
ron2-peptide binding
4
close proximity
4
expressed nicotiana
4
nicotiana benthamiana
4
antibody expressed
4
regions antibody
4
antibody variable
4
proximity ron2-peptide
4
variable regions
4
sorted b-lymphocytes
4

References

(Supplied by CrossRef)

R Fendel et al.
PLoS One 2010

R Ramasamy et al.
Biochim Biophys Acta 1998

KP Day et al.
Immunology today 1991

R Dzikowski et al.
Current genetics 2009

J Langhorne et al.
Nature immunology 2008

MM Elloso et al.
Journal of immunology (Baltimore, Md.: 1950) 1994

G Costa et al.
Blood 2011

G Corradin et al.
Frontiers in immunology 2014

JK Baird et al.
Parasitol Today 1995

K Chelimo et al.
Pediatr Infect Dis J 2005

FaithHA Osier et al.
Infection and immunity 2008

Similar Publications