Post-Vaccination and Post-Infection Immunity to the Hepatitis B Virus and Circulation of Immune-Escape Variants in the Russian Federation 20 Years after the Start of Mass Vaccination.

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018-2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018-2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination.

Dynamic Changes in Hepatitis A Immunity in Regions with Different Vaccination Strategies and Different Vaccination Coverage.

The data on hepatitis A virus (HAV) seroprevalence are critical for the implementation of a universal mass vaccination (UMV) strategy. The latter has not been implemented in Russia; however, regional child vaccination programs have been adopted in some parts of the country. The aim of this study is to assess changes in HAV immunity within the last decade in regions of Russia with different vaccination strategies and different vaccination coverage rates. In regions where UMV has not been implemented and HAV vaccination coverage rates do not exceed the national average, the 50% seroprevalence threshold has shifted in the Moscow region from people aged under 40 years in 2008 to people aged over 59 years in 2020, and from people aged under 30 years to people aged over 40 years in the Khabarovsk region. In two regions (Yakutia and Sverdlovsk), a two-dose-based UMV scheme has been in place since 2011 and 2003, respectively, and in Tuva single-dose child immunization was launched in 2012. These regional programs have resulted in a significant increase in HAV seroprevalence in children and adolescents. In Yakutia, 50% herd immunity had been achieved by 2020 in age groups under 20 years, compared to 20−30% seroprevalence rates in 2008. In the Sverdlovsk region, HAV immunity has increased to >65% over the decade in children aged over 10 years, adolescents and young adults, whereas it declined in older age groups. However, a three-fold drop in HAV immunity has occurred in children under 10 years of age, reflecting a significant decline in vaccination coverage. In Tuva, HAV immunity rates in children under 10 years old increased two-fold to exceed 50% by 2020. These data suggest that UMV should be implemented on a national level. Measures to control vaccination coverage and catch-up vaccination campaigns are recommended in order to maintain the effectiveness of existing HAV vaccination programs.

Ability of inactivated vaccines based on far-eastern tick-borne encephalitis virus strains to induce humoral immune response in originally seropositive and seronegative recipients.

Tick-borne encephalitis (TBE) remains one of the major public health concerns in northern Eurasia, and its' area is expanding. TBE virus (TBEV) includes three subtypes and several monophyletic groups, cocirculating in Russia. Five inactivated vaccines are used for TBE prophylaxis. The rising number of people subjected to vaccination brings up the issue of the impact of individual recipient characteristics on vaccination efficacy. The present work studies correlations among the vaccination scheme, sex, age, body mass index (BMI), chronic diseases, postvaccinal reaction, pre-existing anti-TBEV antibodies, and postvaccinal humoral immunity development. Sera were collected during clinical trials in the TBEV Siberian subtype endemic area. Adult recipients were vaccinated with Tick-E-Vac and EnceVir vaccines based on Far-Eastern TBEV strains. Vaccine ability to induce humoral immunity in different categories of recipients was estimated by seroconversion rates and the percentage of recipients with high neutralizing antibody titers (≥1:500). High immunogenicity of vaccines based on Far-Eastern TBEV strains in the TBEV Siberian subtype endemic area in all groups of recipients was demonstrated. Impact of pre-existing contact with the virus and high BMI on humoral immune response development 14 days after the first immunization was evidenced. Nevertheless, the difference was significantly less pronounced 30 days after the first vaccination and undetectable after the second one.

Comparison of the Immunogenicity and Safety of Two Pediatric TBE Vaccines Based on the Far Eastern and European Virus Subtypes.

Up to 10,000 cases of tick-borne encephalitis are registered annually, 20% of which occur in children under 17 years of age. A comparison of the immunogenicity and safety between a new pediatric Tick-E-Vac vaccine based on the TBEV strain Sofjin and FSME-IMMUN Junior vaccine was performed in the Sverdlovsk region. The vaccine strains differ from strains of the Siberian subtype of TBEV that dominates in the region. The study was performed on 163 children aged 1 to 15, who received one of the vaccines according to either a conventional or rapid vaccination schedule. Immunogenicity was assessed based on the seroprotection rates and titers of virus-neutralizing antibodies. There were no significant differences in either the immunogenicity or reactogenicity of the pediatric vaccines based on strains of the Far Eastern or European subtypes of TBEV. Under both vaccination schedules, 30 days after the second injection, seroprotection rates were 100% for Tick-E-Vac and greater than 95% for FSME-IMMUN Junior, while the geometric mean titer of TBEV-neutralizing antibodies was at least 2,4 log10 (1 : 250) for either vaccine. Fourteen days after the second injection according to the rapid schedule, seroprotection rates were significantly lower, ranging from 50% to 63% regardless of the vaccine used. The observed adverse reactions were mild or moderate for both vaccines under both vaccination schedules, with total adverse event rates of less than 25%. Reactogenicity was not associated with the gender or age of the recipients. There were no statistically significant differences in the incidence of adverse reactions between the group of subjects who were baseline seronegative or seropositive. However, 14 days after the second vaccine injection according to the rapid schedule, a statistically significant difference in nAbs titers was identified between groups of children with and without reported reactions.