SUMMARY Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system diseases in humans.General infection leads to the development of meningitis or encephalitis, which is characterized by swelling of the brain due to inflammation. Tetracyclines may act locally to moderate inflammation in the CNS. In this study, we investigated the potential clinical benefits of administering tetracycline hydrochloride to patients hospitalized due to suspected TBEV infection presenting with fever and evidence of a recent tick bite. We also characterized an acute immune response to TBEV by profiling certain cytokines and soluble receptors in Tetracycline-treated and untreated patients. Increased serum levels of TNF-a , IL-1 a and IL-6 were found in all patients at admission.Soluble receptors presented in the serum of patients in a magnitude higher levels than the corresponding cytokines and were increasing during first weak of hospitalization. Levels of IL-10 were also rising during that period. In our study tetracycline hydrochloride acted as an immunomodulator, which was able to reduce manifestations of inflammation response during TBE course; this action led to quicker improvement of symptoms and, consequently, to a faster clinical recovery. The positive result of tetracycline hydrochloride treatment was accompanied by certain particularities in the dynamics of studyied cytokines and receptors: the concentrations of IL-6, IL-1 b , TNF-a dropped quicker and reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased faster and reached higher maximum levels in the tetracycline-treated groups. Children had the highest levels of IL-6, which were not neurotoxic.
Chikungunya fever is an acute infectious disease caused by the mosquito-borne Chikungunya virus (CHIKV). In the last decades, cases of the disease have been reported in more than 100 countries; therefore, CHIKV presents a global public health problem. CHIKV genotypes have limited antigenic diversity, and documented reinfection is very rare. Hence, a vaccine could prevent infection and potential disability, as well as reduce the epidemic spread of CHIKV in the population.The aim of the study was to review approaches to the development of preventive vaccines against CHIKV, evaluate promising vaccine candidates in preclinical or clinical development stages, and analyse perspectives and challenges of bringing these vaccines to the pharmaceutical market.According to the literature reviewed, both traditional and modern platforms are used in the development of CHIKV vaccines, which has been ongoing for several decades. Each platform has its advantages and limitations. The most popular platforms are live attenuated vaccines and vaccines with viral vector constructs. To date, about 25 vaccine candidates have successfully passed through preclinical studies, and more than 7 vaccine candidates have progressed to various phases of clinical studies. The preventive medicinal products that have reached the clinical development stage include 4 live attenuated vaccines, 1 inactivated vaccine, 1 vaccine containing virus-like particles, and 1 mRNA vaccine. All 7 candidates have demonstrated cross-protection against multiple genotypes of CHIKV at the level of either preclinical in vivo studies and/or clinical in vitro studies. The research continues, and this shows that not only the scientific community but also health systems are interested in bringing effective CHIKV vaccines to the pharmaceutical market.
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.
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