New Russian Trivalent Hepatitis B vaccine (Bubo^®-Unigep): Phase I Clinical Study Results and Perspectives of Further Investigations Aiming Registration in Russia

Abstract

Relevance. The absence of a registered vaccine against G145R escape mutant determines the need to develop a drug for the prophylaxis of infectious hepatitis caused by the hepatitis B virus.The aim of the study was to evaluate the safety and reactogenicity of a new hepatitis B recombinant Bubo®-Unigep yeast vaccine in healthy volunteers.Materials & Methods. To confirm the safety of the new trivalent Bubo®-Unigep vaccine, an open, single- center, nonrandomized clinical trial was conducted in healthy male volunteers at the clinical base of «Uromed» (Smolensk) according to the protocol developed by the contract research organization R&D Pharma.Results and discussions. Safety and reactogenicity assessment was carried out throughout the study period. In the safety assessment, one adverse event was reported that was not related to the use of Bubo®-Unigep vaccine. No serious adverse events have been reported. There were no local reactions at the injection site throughout the observation period. The results indicate a high safety and areactogenicity of Bubo®-Unigep vaccine.Conclusions: The confirmed safety and areactogenicity of a new Bubo®-Unigep vaccine in a phase I clinical trial allows to proceed to the next stage and to conduct a registration study in which immunogenicity, safety and reactogenicity will be studied during the full course of vaccination. The introduction of such a vaccine on the market will contribute to a more effective vaccination against those serotypes of the hepatitis B virus that are endemic and prevail in the Russian Federation. Due to the created complete immunity, the infection threshold rises and the number of cases of hepatitis B among the already vaccinated population decreases.

Vaccine escape challenges virus prevention: The example of two vaccine‐preventable oncogenic viruses

“…In 2019, a new trivalent Hepatitis B vaccine (Bubo ® -Unigep) containing three HBsAgs that confer protection against two broad forms of HBV subtypes and G145R mutant was designed in Russia. 65 However, evidence also demonstrated distinct immunogenic properties of the G145R mutant compared with wild-type. 37 The trivalent vaccine's immunogenicity and safety, especially the G145R mutated HBsAg, need further research.…”

Recombinant HBsAg of the Wild-Type and the G145R Escape Mutant, included in the New Multivalent Vaccine against Hepatitis B Virus, Dramatically Differ in their Effects on Leukocytes from Healthy Donors In Vitro

“…The studies used wild-type rHBsAg of the ayw2 subtype and rHBsAg with the G145R mutation of the ayw2 subtype, both expressed in the yeast H. polymorpha (CJSK "RPC "COMBIOTECH", Moscow, Russia) [4,39,41,42]. The purity of the antigen preparations, determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by Coomassie staining, was more than 85%.…”

“…At present, the most widely used hepatitis B vaccines are second-generation vaccines comprising S-HBsAg of ayw, adw and adr subtypes expressed in different yeast strains, and formulated with either aluminum hydroxide or aluminum hydroxyphosphate sulfate as adjuvants. Second-generation vaccines are mostly HBsAg-monovalent (including one of the aforementioned wild-type subtypes), although some are HBsAg-bivalent (including a combination of S-HBsAg ayw and adw subtypes or S-HBsAg and M-HBsAg of adr subtype) [3,4]. Furthermore, second-generation HBV vaccines are also used as components of combined vaccines containing antigens of other pathogens, including hepatitis A virus, Bordetella pertussis, Corynebacterium diphtheriae, Clostridium tetani, Poliovirus hominis, and Haemophilus influenzae type B. Additionally, there is a hepatitis B vaccine containing S-HBsAg synthesized in Hansenula polymorpha, formulated with a Toll-like receptor 9 (TLR 9) agonist, cytidine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) 1018, as an adjuvant.…”

“…The urgency of the problem, however, dictates the need for developing a vaccine that would elicit a protective humoral immune response against both individual HBV subtypes (ay and ad) and epitopes of the G145R and other escape mutants. It is expected that by expanding the specificity of the immune response, such a new-generation, multivalent vaccine will significantly increase the effectiveness of vaccination against HBV [4]. Given the aforementioned features of the G145R mutant HBsAg folding, the recombinant analogue of the antigen included in the vaccine should have the same biological activity.…”

“…The preliminary selection of rHBsAg containing the G145R mutation, similar to the native analogue in antigenic and immunogenic properties, allowed for developing a component of the hepatitis B vaccine with the G145R escape mutation in HBsAg [39]. In 2019, CJSK "RPC COMBIOTECH" designed a new trivalent vaccine Bubo ® -Unigep, containing antigens that confer protection against wild forms of HBV subtypes ay and ad, as well as a determinant of serotype ay with the G145R mutation at 10 µg/mL of suspension [4]. Currently, Phase III clinical evaluation of this vaccine is approaching completion.…”