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Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus
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نویسنده
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pal p. ,dowd k.a. ,brien j.d. ,edeling m.a. ,gorlatov s. ,johnson s. ,lee i. ,akahata w. ,nabel g.j. ,richter m.k.s. ,smit j.m. ,fremont d.h. ,pierson t.c. ,heise m.t. ,diamond m.s.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 4
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چکیده
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Chikungunya virus (chikv) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. as there is a pressing need for the development of therapeutic agents,we screened 230 new mouse anti-chikv monoclonal antibodies (mabs) for their ability to inhibit infection of all three chikv genotypes. four of 36 neutralizing mabs (chk-102,chk-152,chk-166,and chk-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type i ifn receptor (ifnar-/-) and mapped to distinct epitopes on the e1 and e2 structural proteins. chk-152,the most protective mab,was humanized,shown to block viral fusion,and require fc effector function for optimal activity in vivo. in post-exposure therapeutic trials,administration of a single dose of a combination of two neutralizing mabs (chk-102+chk-152 or chk-166+chk-152) limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before chikv-induced death. selected pairs of highly neutralizing mabs may be a promising treatment option for chikv in humans.
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آدرس
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department of molecular microbiology,washington university school of medicine,st. louis,mo, United States, viral pathogenesis section,laboratory of viral diseases,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, department of medicine,washington university school of medicine,st. louis,mo, United States, department of biochemistry and molecular biophysics,washington university school of medicine,st. louis,mo, United States, macrogenics,rockville,md, United States, macrogenics,rockville,md, United States, department of medicine,washington university school of medicine,st. louis,mo, United States, vaccine research center,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, vaccine research center,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, department of medical microbiology,molecular virology section (hpc eb88),university medical center groningen,university of groningen,groningen, Netherlands, department of medical microbiology,molecular virology section (hpc eb88),university medical center groningen,university of groningen,groningen, Netherlands, department of biochemistry and molecular biophysics,washington university school of medicine,st. louis,mo,united states,department of pathology and immunology,washington university school of medicine,st. louis,mo, United States, viral pathogenesis section,laboratory of viral diseases,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, department of genetics,university of north carolina at chapel hill,chapel hill,nc, United States, department of molecular microbiology,washington university school of medicine,st. louis,mo,united states,department of medicine,washington university school of medicine,st. louis,mo,united states,department of pathology and immunology,washington university school of medicine,st. louis,mo, United States
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Authors
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