Cross-reactivity of hantavirus antibodies after immunization with PUUV antigens.

Nephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross-reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross-reactive with serum from MVs immunized small mammals. These cross-reactive epitopes were located in oligomerization perinuclear targeting and Daxx-interacting domains. Most cross-reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross-reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE.

Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia.

Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the "Russia" (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.