Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Antibodies, Viral/*blood ; Encephalitis Virus, Japanese/*immunology ; Enzyme-Linked Immunosorbent Assay/*methods; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Antibody Specificity ; Child ; Conserved Sequence ; Cross Reactions ; Dengue/immunology ; Dengue/virology ; Dengue Virus/classification ; Dengue Virus/genetics ; Dengue Virus/immunology ; Encephalitis Virus, Japanese/genetics ; Encephalitis, Japanese/epidemiology ; Encephalitis, Japanese/immunology ; Encephalitis, Japanese/virology ; Enzyme-Linked Immunosorbent Assay/statistics & numerical data ; Female ; Healthy Volunteers ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; Peptide Fragments/genetics ; Peptide Fragments/immunology ; Sensitivity and Specificity ; Seroepidemiologic Studies ; Serogroup ; Sri Lanka/epidemiology ; Vaccination ; Viral Proteins/genetics ; Viral Proteins/immunology ; Young Adult

Introduction: Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity.
Methodology and Results: 22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3).
Conclusions: As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.
Competing Interests: The authors have declared that no competing interests exist.

Vet J. 2013 Jan;195(1):33-40. (PMID: 23036176)
J Gen Virol. 2011 Dec;92(Pt 12):2821-2829. (PMID: 21900425)
PLoS One. 2015 Dec 22;10(12):e0144799. (PMID: 26696417)
Viruses. 2011 Dec;3(12):2374-95. (PMID: 22355444)
Annu Rev Entomol. 2009;54:17-35. (PMID: 19067628)
Clin Diagn Lab Immunol. 1998 Jan;5(1):7-10. (PMID: 9455871)
Vaccine. 2017 Nov 7;35(47):6355-6358. (PMID: 29029938)
PLoS Negl Trop Dis. 2013 Jul 11;7(7):e2311. (PMID: 23875046)
Microbes Infect. 2002 Oct;4(12):1209-15. (PMID: 12467761)
Clin Exp Immunol. 2012 May;168(2):215-23. (PMID: 22471283)
Methods Mol Biol. 2018;1808:165-171. (PMID: 29956182)
J Infect Dis. 2009 Dec 15;200(12):1893-900. (PMID: 19911991)
PLoS Negl Trop Dis. 2011 Oct;5(10):e1311. (PMID: 21991398)
Lancet. 2012 Nov 3;380(9853):1535-6. (PMID: 22975339)
mBio. 2018 Feb 27;9(1):. (PMID: 29487230)
J Virol. 2003 Feb;77(4):2600-6. (PMID: 12551998)
PLoS Negl Trop Dis. 2017 May 15;11(5):e0005554. (PMID: 28505154)
Front Public Health. 2020 Feb 12;8:19. (PMID: 32117854)
PLoS Negl Trop Dis. 2017 Sep 21;11(9):e0005866. (PMID: 28934197)
Nature. 2013 Apr 25;496(7446):504-7. (PMID: 23563266)
J Virol. 2008 Jul;82(14):7009-21. (PMID: 18480437)
Curr Opin Infect Dis. 2010 Oct;23(5):426-31. (PMID: 20581670)
PLoS Negl Trop Dis. 2015 Apr 13;9(4):e0003673. (PMID: 25875020)
BMC Infect Dis. 2016 Jul 08;16:319. (PMID: 27391896)
Am J Trop Med Hyg. 1999 Apr;60(4):693-8. (PMID: 10348250)
BMC Infect Dis. 2016 Oct 18;16(1):578. (PMID: 27756212)
Biologics. 2013;7:175-87. (PMID: 23983454)
Sci Rep. 2016 Jan 28;6:19953. (PMID: 26818736)
Int J Gen Med. 2009 Dec 29;2:195-200. (PMID: 20360904)

0 (Antibodies, Viral)
0 (Immunoglobulin G)
0 (Peptide Fragments)
0 (Viral Proteins)

Date Created: 20201028 Date Completed: 20201116 Latest Revision: 20201116

20240104

PMC7592747

10.1371/journal.pone.0238609

33112881