Analysis of humoral immune responses in #chikungunya virus (CHIKV) infected patients and individuals vaccinated with a candidate CHIKV #vaccine (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Analysis of humoral immune responses in chikungunya virus (CHIKV) infected patients and individuals vaccinated with a candidate CHIKV vaccine

Lisa Henss, Constanze Yue, Christine von Rhein, Roland Tschismarov, Lia Laura Lewis-Ximenez, Albert Dölle, Sally A Baylis, Barbara S Schnierle

The Journal of Infectious Diseases, jiz658, https://doi.org/10.1093/infdis/jiz658

Published: 12 December 2019

 

Abstract

Background

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu like symptoms. The acute symptoms disappear after one week, but chronic arthralgia can persist for years. Here, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed.

Methods

Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors and antibody epitope mapping was performed with a peptide array.

Results

Greatest CHIKV neutralization activity was observed 60-92 days after onset of symptoms. The amount of CHIKV-specific antibodies, their binding avidity and cross-reactivity with other alphaviruses increased over time. CHIKV and o’nyong-nyong virus (ONNV) were both neutralized to a similar extent. Linear antibody binding epitopes were mainly found in E2 domain B and the acid-sensitive regions (ASRs). In addition, serum samples from healthy volunteers vaccinated with a measles-vectored chikungunya vaccine candidate, MV-CHIK, were analyzed. Neutralization activity in the samples from the vaccine cohort was 2–6-fold lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination only induced cross-neutralization with ONNV and the E2 ASR1 was the major antibody target.

Conclusion

These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.

alphavirus, chikungunya, antibody, neutralization

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This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Chikungunya fever; Alphavirus; o’nyong-nyong virus; Vaccines.

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#Chikungunya and O’nyong-nyong Viruses in #Uganda: Implications for Diagnostics (Open Forum Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Open Forum Infect Dis. 2019 Jan 3;6(3):ofz001. doi: 10.1093/ofid/ofz001. eCollection 2019 Mar.

Chikungunya and O’nyong-nyong Viruses in Uganda: Implications for Diagnostics.

Clements TL1, Rossi CA1, Irish AK2, Kibuuka H3, Eller LA3, Robb ML4, Kataaha P5, Michael NL6, Hensley LE7, Schoepp RJ1.

Author information: 1 US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland. 2 College of Public Health, University of Iowa, Iowa City, Iowa. 3 Makerere University Walter Reed Project, Kampala, Uganda. 4 Henry M. Jackson Foundation, Rockville, Maryland. 5 Nakasero Blood Bank, Kampala, Uganda. 6 Walter Reed Army Institute of Research, Rockville, Maryland. 7 National Institute of Allergy and Infectious Diseases-Integrated Research Facility, Frederick, Maryland.

 

Abstract

BACKGROUND:

A serosurvey of healthy blood donors provided evidence of hemorrhagic fever and arthropod-borne virus infections in Uganda.

METHODS:

Antibody prevalence to arthropod-borne and hemorrhagic fever viruses in human sera was determined using enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT).

RESULTS:

The greatest antibody prevalence determined by ELISA was to chikungunya virus (CHIKV) followed in descending order by West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Ebola virus (EBOV), dengue virus (DEN), yellow fever virus (YFV), Rift Valley fever virus (RVFV), Marburg virus (MARV), and Lassa virus (LASV). Further investigation of CHIKV-positive sera demonstrated that the majority of antibody responses may likely be the result of exposure to the closely related alphavirus o’nyong-nyong virus (ONNV).

CONCLUSIONS:

As the use of highly specific and sensitive polymerase chain reaction-based assays becomes the diagnostic standard without the corresponding use of the less sensitive but more broadly reactive immunological-based assays, emerging and re-emerging outbreaks will be initially missed, illustrating the need for an orthogonal system for the detection and identification of viruses causing disease.

Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019.

KEYWORDS: CHIKV; ONNV; Uganda; chikungunya; diagnostics; o’nyong-nyong; serosurvey

PMID: 31660384 PMCID: PMC6411207 [Available on 2020-01-03] DOI: 10.1093/ofid/ofz001

Keywords: Alphavirus; Chikungunya fever; O’nyong-nyong virus; Serosurvey; Uganda.

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Src Family #Kinase Inhibitors Block Translation of #Alphavirus Subgenomic mRNAs (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Src Family Kinase Inhibitors Block Translation of Alphavirus Subgenomic mRNAs

Rebecca Broeckel, Sanjay Sarkar, Nicholas A. May, Jennifer Totonchy, Craig N. Kreklywich, Patricia Smith, Lee Graves, Victor R. DeFilippis, Mark Heise, Thomas E. Morrison,Nathaniel Moorman, Daniel N. Streblow

DOI: 10.1128/AAC.02325-18

 

ABSTRACT

Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts. Based upon the results of this study, we treated CHIKV infected cells with kinase inhibitors targeting the SFK-PI3K-AKT-mTORC signaling pathways. Treatment of cells with Src Family Kinase (SFK) inhibitors blocked the replication of CHIKV, as well as multiple other alphaviruses including Mayaro virus, o’nyong-nyong virus, Ross River virus, and Venezuelan equine encephalitis virus. Dissecting the effect of SFK inhibition on alphavirus replication, we found that viral structural protein levels were significantly reduced, but synthesis of viral genomic and subgenomic RNAs was unaffected. By measuring the association of viral RNA with polyribosomes we found that the SFK inhibitor dasatinib blocks alphavirus subgenomic RNA translation. Our results demonstrate a role for SFK signaling in alphavirus subgenomic RNA translation and replication. Targeting host factors involved in alphavirus replication represents an innovative, perhaps paradigm-shifting strategy for exploring replication of CHIKV and other alphaviruses, while promoting antiviral therapeutic development.

Copyright © 2019 Broeckel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Arbovirus; Alphavirus; Chikungunya fever; Viral pathogenesis.

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