Although unprecedented efforts aiming to stop the COVID-19 pandemic have been made over the past two years, SARSCoV-2 virus still continues to cause intolerable health and economical losses. Vaccines are considered the most effective way to prevent infectious diseases, which has been reaffirmed for COVID-19. However, in the context of the continuing virus spread because of insufficient vaccination coverage and emergence of new variants of concern, there is a high demand for vaccination strategy amendment. The ability to elicit protective immunity at the entry gates of infection provided by mucosal vaccination is key to block virus infection and transmission. Therefore, these mucosal vaccines are believed to be a “silver bullet” that could bring the pandemic to an end. Here, we demonstrate that the intranasally delivered Gam-COVID-Vac (Sputnik V) vaccine induced a robust (no less than 180 days) systemic and local immune response in mice. High immunogenic properties of the vaccine were verified in non-human primates (common marmosets) by marked IgG and neutralizing antibody (NtAb) production in blood serum, antigen-specific Tcell proliferation and cytokine release of peripheral blood mononuclear cells accompanied by formation of IgA antibodies in the nasal mucosa. We also demonstrate that Sputnik V vaccine can provide sterilizing immunity in K18-hACE2 transgenic mice exposed to experimental lethal SARS-CoV-2 infection protecting them against severe lung immunopathology and mortality. We believe that intranasal Sputnik V vaccine is a promising novel needle-free mucosal vaccine candidate for primary immunization as well as for revaccination and is worth further clinical investigation.

Tick-borne encephalitis virus (TBEV) and Powassan virus (POWV) are neurotropic tick-borne orthoflaviviruses. They cause mostly asymptomatic infections in hosts, but severe forms with CNS involvement can occur. Studying the early stages of viral infections in humans is challenging, and appropriate animal models are essential for understanding the factors determining the disease severity and for developing emergency prophylaxis and treatment options. In this work, we assessed the model of the early stages of TBEV and POWV mono- and co-infections in Macaca fascicularis. Serological, biochemical, and virological parameters were investigated to describe the infection, including its impact on animal behavior. Viremia, neutralizing antibody dynamics, and viral load in organs were chosen as the main parameters distinguishing early-stage orthoflavivirus infection. Levels of IFNα, monocyte count, and cognitive test scores were proposed as additional informative indicators. An assessment of a tick-borne encephalitis vaccine using this model showed that it provided partial protection against POWV infection in Macaca fascicularis without signs of antibody-dependent enhancement of infection.

Ranges of distribution of some orthoflaviviruses, including the Omsk hemorrhagic fever virus (OHFV) and the Powassan virus (POWV), have been identified in the range endemic for the tick-borne encephalitis virus (TBEV). In contrast to TBEV, no registered vaccine against OHFV and POWV is currently available. Nevertheless, recent studies have indicated that the anti-TBEV vaccine may offer partial protection against other orthoflaviviruses. The present study assesses OHFV and POWV infection in an experimental model on BALB/c mice one, three- and twelve-months post-immunization with inactivated TBE vaccine. The TBE vaccine was shown to provide long-term protection against OHFV and partial protection against POWV, even in the absence of specific antibodies, and without indications of antibody-dependent enhancement of infection. The neutralizing antibody titer for OHFV in vaccinated animals before and after the challenge with OHFV was similar to the titer of antibodies against the TBEV vaccine strain. Following immunization with anti-TBEV vaccine and subsequent inoculation of POWV, the levels of neutralizing antibodies against the TBEV vaccine strain was observed to be higher compared to those targeting POWV, especially during the initial phase of infection. Such cross-reactive antibodies have potential to pose a significant diagnostic challenge in cases where an infection is occurring simultaneously with an immune response to another virus.