Mouse and Human Monoclonal Antibodies Protect against Infection by Multiple Genotypes of Japanese Encephalitis Virus

MBio
Estefania FernandezMichael S Diamond

Abstract

Japanese encephalitis virus (JEV) remains a leading cause of viral encephalitis worldwide. Although JEV-specific antibodies have been described, an assessment of their ability to neutralize multiple genotypes of JEV has been limited. Here, we describe the development of a panel of mouse and human neutralizing monoclonal antibodies (MAbs) that inhibit infection in cell culture of four different JEV genotypes tested. Mechanism-of-action studies showed that many of these MAbs inhibited infection at a postattachment step, including blockade of virus fusion. Mapping studies using site-directed mutagenesis and hydrogen-deuterium exchange with mass spectrometry revealed that the lateral ridge on domain III of the envelope protein was a primary recognition epitope for our panel of strongly neutralizing MAbs. Therapeutic studies in mice demonstrated protection against lethality caused by genotype I and III strains when MAbs were administered as a single dose even 5 days after infection. This information may inform the development of vaccines and therapeutic antibodies as emerging strains and genotypic shifts become more prevalent.IMPORTANCE Although Japanese encephalitis virus (JEV) is a vaccine-preventable cause of viral encephalitis, ...Continue Reading

References

Jul 1, 1992·The American Journal of Tropical Medicine and Hygiene·W R ChenR B Tesh
Jan 11, 1992·Epidemiologic Reviews·D W Vaughn, C H Hoke
Dec 1, 1990·The Journal of General Virology·W R ChenR Rico-Hesse
Mar 23, 2000·Journal of Neurology, Neurosurgery, and Psychiatry·T SolomonV T Khanh
Apr 27, 2005·Nature Medicine·Theodore OliphantMichael S Diamond
May 26, 2005·Protein Expression and Purification·F William Studier
Sep 30, 2005·Nature·Grant E NybakkenDaved H Fremont
Sep 22, 2006·Journal of Virology·Grant E NybakkenDaved H Fremont
Feb 28, 2007·The Journal of General Virology·Huan Yu WangGuo Dong Liang
Aug 3, 2007·Journal of Virology·Karin StiasnyFranz X Heinz
May 13, 2008·Expert Reviews in Molecular Medicine·Theodore C Pierson, Michael S Diamond
Mar 25, 2010·PLoS Pathogens·Wahala M P B WahalaAravinda M de Silva
May 14, 2010·Clinical and Vaccine Immunology : CVI·Stanley A Plotkin
Aug 13, 2010·Journal of Virology·James D BrienMichael S Diamond
Mar 1, 2011·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Manal A F MohammedTom Solomon
Jul 1, 2011·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Jani BorahJagadish Mahanta
Sep 29, 2011·Virology Journal·Ratree TakhampunyaBrian P Evans
Nov 16, 2011·Bulletin of the World Health Organization·Grant L CampbellAmy S Ginsburg
Dec 14, 2011·Journal of Virology·Vincent C LucaDaved H Fremont
Jun 14, 2012·Journal of the American Society for Mass Spectrometry·Bruce D PascalPatrick R Griffin
Mar 23, 2013·The Journal of Veterinary Medical Science·Hiroshi ShimodaKen Maeda
Jul 3, 2013·PLoS Pathogens·Oksana VratskikhFranz X Heinz
Sep 7, 2013·PLoS Neglected Tropical Diseases·Amy J SchuhAlan D T Barrett
Feb 11, 2014·Current Protocols in Microbiology·James D BrienMichael S Diamond

❮ Previous
Next ❯

Citations

Nov 30, 2018·Immunology·Rachel Wong, Deepta Bhattacharya
Jan 17, 2020·PLoS Pathogens·Anna BuchmanOmar S Akbari
Jul 25, 2019·The Journal of Experimental Medicine·James T EarnestMichael S Diamond
Feb 19, 2019·Antibodies·Siva Krishna AngalakurthiNicholas J Mantis
Nov 20, 2019·International Journal of Molecular Sciences·Yu-Qin CaoSan-Jie Cao
May 6, 2020·Nature Microbiology·Theodore C Pierson, Michael S Diamond
Jan 7, 2021·Analytical and Bioanalytical Chemistry·Haofeng SunDewei Song
Apr 9, 2021·The Journal of Experimental Medicine·Laura A VanBlarganMichael S Diamond
Jul 19, 2021·Molecular Aspects of Medicine·Kiran Bala SharmaManjula Kalia
Dec 5, 2020·Analytical Chemistry·Tobias P WörnerAlbert J R Heck

❮ Previous
Next ❯

Methods Mentioned

BETA
flow
enzyme-linked immunosorbent assay
ELISA
flow cytometry
X-ray
density gradient centrifugation

Software Mentioned

FlowJo
Genewiz
MassMatrix
MacsQuant
HDX workbench

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Antibody Repertoire Diversity

Antibody repertoire diversity and its role during natural infection is a prerequisite for molecular and structural elucidation of functionally protective immunity. Discover the latest insights into antibody diversity here.