Evervac: phase I/II study of immunogenicity and safety of a new adjuvant-free TBE vaccine cultivated in Vero cell culture

Abstract

Approximately 10,000 cases of tick-borne encephalitis (TBE), a serious disease of the central nervous system caused by tick-borne encephalitis virus (TBEV), are registered worldwide every year. Vaccination against TBE remains the most essential measure of preventing the disease. Unlike available TBE vaccines, a new inactivated lyophilized candidate vaccine Evervac is produced in Vero continuous cell culture and its final formulation does not include aluminum-based adjuvants. To study the safety and immunogenicity of Evervac, healthy adults 18-60 y of age were immunized twice at 30-d intervals. The study was singleblind, randomized, comparative, controlled, and was conducted in TBE-endemic areas. The commercial lyophilized vaccine TBE-Moscow was used as a comparison treatment. The subjects were observed for incidence, severity, and duration of adverse reactions. It was shown that the severity of local and systemic reactions in the Evervac vaccine group was mild to moderate. There were no significant differences in the incidence of adverse reactions between the Evervac and TBE-Moscow vaccine groups. Immunization with Evervac produced a significant increase in geometric mean titer (GMT) of anti-TBEV antibodies in both initially seronegative and seropositive recipients. The seroconversion rate for the initially seronegative recipients was 69% (GMT = 1:214) after the first dose and reached 100% after the second dose. In these parameters, there were no significant differences between the study and control vaccine groups. Thus, the adjuvant-free Vero-based vaccine Evervac was well tolerated, had low reactogenicity, induced a pronounced immune response, and was overall non-inferior to the commercial adjuvanted TBE vaccine used as a control.

Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies

“…The structure of the production process of the vaccine CoviVac ( Figure 1 (A)) is rather similar to the ones presented for other inactivated vaccines against COVID-19 [ 26–28 ]. Beta-propiolactone was used to shorten the production process.…”

“…The drastic global shortage of the COVID-19 vaccines and successful clinical trials of the several inactivated preparations make this approach appropriate for inactivated vaccine producers. The Chumakov Center has successfully developed two inactivated vaccines on Vero cells against tick-borne encephalitis and poliomyelitis [22,23]. Therefore, the development of the COVID-19 vaccine was based on the established cell cultivating platform using previously established methods.…”

Flavivirus: From Structure to Therapeutics Development

“…In addition, it differs from the available vaccines, Evervac vaccine is absence of aluminum hydroxide adjuvant. Animal experiments have shown that the application of this vaccine can significantly increase the geometric mean titer (GMT) of anti-TBEV antibodies in serum, and this vaccine has been proven to be safe and effective in the phase II of clinical study [ 112 ]. These valuable attempts suggest that factors of both pathogens and hosts should be evaluated in vaccine development.…”

Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise

“…Recently, an aluminum hydroxide-free, inactivated whole virus TBEV vaccine (Evervac, TBEV-FE strain Sofjin) produced in a continuous Vero cell line was tested in a phase I/II clinical trial and showed comparable safety, tolerability and immunogenicity results to the TBE vaccine Moscow. However, this vaccine is not yet licensed [ 41 ]. The vaccination schedules of the TBEV vaccines are very time-consuming.…”