In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments

被引:27
作者
Aladin, Farah [1 ]
Einerhand, Alexandra W. C. [2 ]
Bouma, Janneke [2 ]
Bezemer, Sandra [3 ]
Hermans, Pim [3 ]
Wolvers, Danielle [4 ]
Bellamy, Kate [5 ]
Frenken, Leon G. J. [4 ]
Gray, Jim [1 ]
Iturriza-Gomara, Miren [1 ]
机构
[1] Hlth Protect Agcy, Ctr Infect, Enter Virus Unit, London, England
[2] Erasmus MC Sophia, Pediat Lab, Rotterdam, Netherlands
[3] BAC BV, Naarden, Netherlands
[4] Unilever Res & Dev Vlaardingen BV, Vlaardingen, Netherlands
[5] Unilever Res & Dev Colworth House, Sharnbrook, Beds, England
关键词
MONOCLONAL-ANTIBODIES; PEDIATRIC POPULATION; CONFER PROTECTION; BOVINE COLOSTRUM; INDUCED DIARRHEA; CHILDREN; IMMUNOGLOBULIN; PROTEIN; GASTROENTERITIS; PATHOGENESIS;
D O I
10.1371/journal.pone.0032949
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/ or treatment of infection of a broad range of clinically relevant rotavirus strains.
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