2010 Fiscal Year Final Research Report
Field trial of human monoclonal antibody cocktails possessing neutralizing ability against rabies virus in Asia
| Project/Area Number |
19406016
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 海外学術 |
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| Research Field |
Virology
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| Research Institution | Oita University |
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Principal Investigator |
NISHIZONO Akira Oita University, 医学部, 教授 (70218155)
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| Co-Investigator(Kenkyū-buntansha) |
AHMED Kamruddin 大分大学, 全学研究推進機構, 准教授 (00398140)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMADA Kentaro 大分大学, 全学研究推進機構, 助教 (70458280)
SENBA Kazuyo 大分大学, 全学研究推進機構, 助教 (30381031)
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| Project Period (FY) |
2007 – 2010
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| Keywords | 狂犬病 / ヒト型単クローン抗体 / 曝露後治療 / アジア |
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| Research Abstract |
Rabies is a fatal viral encephalitis transmitted by exposure to the bite of rabid animals. Although human and equine rabies immunoglobulins are indispensable pharmacological agents for severe bite exposure, as is vaccine, several disadvantages including limited supply, adverse reactions, and high cost hamper their wide application in developing countries. We established two novel human monoclonal antibodies (MAbs) that neutralize rabies virus from vaccinated hyperimmune donors using the Epstein-Barr virus transformation method. One MAb (No. 254) was subclass IgG3, which effectively neutralized fixed rabies viruses of CVS, ERA, HEP-Flury, and Nishigahara strains and recognized a well-conserved epitope located in antigenic site II of the rabies virus glycoprotein. No. 254 possessed 68 ng/ml of 50% focus reduction neutralizing activity against CVS, 3.7x10^<-7> M of the dissociation equilibrium constant, and the enhancing effect of complement-dependent virolysis. In addition, No. 254 showed effective neutralization potency in vivo by the mouse challenge test. The other 4D4 was subclass IgM, showing neutralizing activity against CVS and Nishigahara strains and recognized a novel epitope located between antigenic sites I and VI, which is associated with the neurovirulence of rabies. Both human MAbs against rabies are expected to be utilized as a tool for future post-exposure prophylaxis.
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Research Products
(19 results)
