The study of flaviviruses and Chikungunya virus seroprevalence in Nicaragua — virus-specific antibody avidity assay as a tool for differential diagnosis

Abstract

Introduction. Arboviral infections are a rising public health concern not only for some individual countries, but also for the entire world due to the repeated outbreaks over the past decade.The aim was to conduct a seroprevalence study of Dengue (DENV), Zika (ZIKV), Yellow fever (YFV) and Chikungunya (CHIKV) viruses using a limited number of samples in Nicaragua.Materials and methods. Total 200 serum samples collected previously in Nicaragua were analyzed simultaneously. Commercially available diagnostic kits, as well as in-house methods were used. The avidity of antibodies (IgG) in positive serum samples was assessed after the treatment with 8M urea.Results. 85 serum samples (42.5%) contained IgG antibodies to one or several viruses simultaneously. IgG antibodies only to one virus were detected in 46 serum samples (23%) with the avidity index (AI) ≥ 30%. Among 39 samples (19.5%) that contained IgG antibodies to several viruses, only in 19 samples (9.5%) IgG antibodies with high AI (≥ 30%) to several viruses were detected. In 16 serum samples (8.0%), IgG antibodies to DENV with a high AI and antibodies to ZIKV and/or YFV with a low AI < 30% were detected.Discussion. The results obtained in ELISA testing were corrected, since only IgG antibodies with a high AI confirm the past infection. The analysis of the specific IgG antibody avidity helped not only to confirm the cases of combined or sequential infection in the past, but also to discriminate the cross-reactive IgG antibodies induced by closely related DENV, ZIKV and YFV. The presence of cross-reactive IgG antibodies, on the one hand, make it difficult to determine the real seroprevalence of flavivirus infections, and, on the other hand, may increase the risk of antibody-dependent enhancement (ADE) of the disease, which is well-known for the secondary Dengue fever and for the consecutive infection with DENV and ZIKV.Conclusion. The analysis of virus-specific antibody avidity made it possible not only to distinguish recent from the past infection, but also to discriminate the cross-reactive antibodies with the low avidity.

Recombinant TBEV Protein E of the Siberian Subtype Is a Candidate Antigen in the ELISA Test System for Differential Diagnosis

“…The fourth set of human sera containing antibodies against various orthoflaviviruses was previously described in [34]. The sera were obtained from a double-blind clinical study in which participants gave voluntary, informed consent to the use of sera.…”

“…The specificity of TBE antibody detection in the developed ELISA test system was shown using a pool of human sera of Japanese encephalitis (JE), Zika, West Nile (WN), and dengue patients with clinically and laboratory-confirmed infections (the first set) and containing antibodies to one or several orthoflavi-or alphaviruses previously described in [34] (the fourth set). All the tested sera were negative for the dIII or sE recombinant protein-based ELISA (Table 5).…”

Development of MVA-d34 Tetravalent Dengue Vaccine: Design and Immunogenicity

“…For ELISA and Western blotting, sera from dengue convalescent individuals (without specifying the serotype) or individuals vaccinated with the vaccine against tick-borne encephalitis (TBEV), produced by the Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences, or vaccinated with the yellow fever virus (YFV) vaccine, also produced by the Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, were used. Convalescent sera from DENV-infected individuals were obtained as part of a study of the prevalence of flavivirus-related fevers in Nicaragua [19]. The sera of vaccinated individuals were obtained by assessing the immune status of FMBA employees vaccinated with tick-borne encephalitis and yellow fever vaccines.…”