Characterization of antibody response in patients with acute and chronic chikungunya virus disease
Section snippets
Background
Chikungunya virus (CHIKV) belongs to the genus alphavirus of the Togaviridae family. Following acute infection, 20–50% of patients develop chronic symptoms lasting between weeks to years [1,2]. Both innate and adaptive immunity have been proposed to play a role in the development of chronic disease, but the complete mechanisms are still unclear [3]. Antibodies to CHIKV have been shown to be important for viral clearance and mediate protection against re-infection [4,5]. Although neutralizing
Objectives
To characterize the antibody response in plasma of patients with acute and chronic CHIKV disease.
Patients
This study was a prospective observational study conducted in Curaçao, which is a continuation from a previous report [14]. The selection of patients was based on the availability of clinical symptoms and plasma sample during follow-up. Patients that still experienced chronic symptoms after 3 months (arthralgia and/or myalgia) were defined as “chronic disease” while patients with no symptoms were defined as having had an “acute disease”. IgM/IgG ELISA (IBL, Germany) and qRT-PCR were also
Cohort description
Fifty-two patients were diagnosed with chronic disease and 38 patients with acute disease. The median follow-up time for the sample collection was 12 months (range 3–14 months) for both groups. All follow-up samples were negative for CHIKV RNA and positive for anti−CHIKV IgGs. Three patients showed measurable levels of anti−CHIKV IgM in the follow-up samples, which were taken 12 months (2 patients) and 6 months (1 patient) post-infection. Two patients belonged to the acute group while one
Discussion
This manuscript describes several properties of the antibody response in a cohort of CHIKV patients. Firstly, our data revealed that NABs produced against one genotype of CHIKV are cross-reactive against another genotype. This result is in agreement with the other studies showing complete cross-neutralization [22,23]. The high percentage of amino acid similarity among all CHIKV strains [24] together with minimal differences in vaccine-NAB responses observed among genotypes [25] indicate that
Conclusions
Our results indicate that VNT50 was not different between patients with acute and chronic chikungunya. However, complement increased the neutralization capacity against CHIKV when high amount of virus was used. Finally, the average AI against E1 and E2 glycoproteins was higher in the acute compared to chronic group.
Credit author statement
FA and BEEM conceptualized and designed the study. FA, SML and SF performed the experiments. RW contributed in the sample collections and reagents. FA, SML, SF, RW, ADMEO and BEEM all contributed in the planning of the manuscript, data analysis and interpretion, and critical review and approval of the manuscript.
Ethical approval
Ethical clearance for this study was obtained from the Medical Ethics Committee of Curaçao (ref. no. 2014-003). Written informed consent was obtained from enrolled patients.
Funding
FA was supported by the Directorate of Higher Education (DIKTI) PhD grant of the Ministry of Research, Technology and Higher Education of the Republic of Indonesia. The funders had no role in study design, data collection and analysis, preparation of the manuscript, and decision to publish.
Acknowledgement
The authors would like to thank the physicians, the lab technicians and the patients in Curaçao for their help and support in this study.
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