Analysis of the safety and immunogenicity profile of an azoximer bromide polymer-adjuvanted subunit influenza vaccine.

A systematic review of clinical trials conducted with a low-dose inactivated influenza vaccine adjuvanted by azoximer bromide (AZB, Polyoxidonium), was performed to compare vaccine reactogenicity against non-adjuvant vaccines. We also assessed whether lower amounts of antigen per viral strain in AZB-adjuvanted vaccines affected antibody responses. A robust search strategy identified scientific publications reporting 30 clinical trials, comprising data on 11,736 participants and 86 trial arms, for inclusion in the analysis. Local reaction rates (R lr) appeared to be lower in AZB-adjuvanted vaccine treatment arms versus comparator vaccine treatment arms. Post-vaccination geometric mean titres in those exposed to AZB-adjuvanted vaccine and comparator vaccine treatment arms were similar in both children and adults aged 18-60 years, implying an antigen-sparing effect by AZB. Meta­regression analysis based on a literature search of records or reports of clinical trials featuring AZB and the inactivated subunit of influenza published between 1998-2018 was conducted online in January 2019 and updated in August 2019. This search covered trials performed between 1993 and 2016 and suggested that AZB did not contribute to vaccine reactogenicity.

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy infants, children, and adolescents.

Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV), which can result in bacterial superinfection, central nervous system complications, and hospitalization. Stage 2 of this Phase 3 open-label study (ClinicalTrials.gov identifier: NCT03843632) enrolled 100 healthy infants, children, and adolescents (12 months-6 years, n = 37; 7-12 years, n = 33; 13-17 years, n = 30) without a clinical history of varicella. Participants aged 12 months-12 years were administered 1 dose of VARIVAX™ 0.5 mL (Varicella Virus Vaccine Live [Oka/Merck]) and adolescents aged 13-17 years were administered 2 doses 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immunosorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and VZV antibody geometric mean titers 6 weeks after the final dose. For participants who were VZV seropositive at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by antibody titer geometric mean fold rise and percentage of participants with ≥4-fold rise in antibody titer 6 weeks after the final dose. A Vaccine Report Card was used to report solicited and unsolicited adverse events through 42 days post-vaccination. After series completion among seronegative participants across age groups (n = 74), 98.6% demonstrated seroconversion 6 weeks post-vaccination; among seropositive participants (n = 26), 65.4% had ≥4-fold rise in antibody titer 6 weeks post-vaccination. No new safety signals were observed. Administering VARIVAX to infants, children, and adolescents resulted in an acceptable immune response with a safety profile consistent with the licensed product.

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy adults.

Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV). Adults typically experience more severe symptoms than children and have a higher risk of developing complications. Stage 1 of this Phase 3 open-label study enrolled healthy adults in Russia aged 18-75 years without a clinical history of varicella infection. Eligible participants (n = 50) were administered 2 doses of VARIVAX™ (Varicella Virus Vaccine Live [Oka/Merck]) 0.5 mL 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immuno-sorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and assessment of geometric mean titers of VZV antibody as measured by gpELISA 6 weeks after Dose 2. For VZV seropositive participants at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by geometric mean fold rise in antibody titer and percentage of participants with a ≥ 4-fold rise in antibody titer 6 weeks after Dose 2. A Vaccine Report Card was used to record solicited and unsolicited adverse events through 42 days post-vaccination. All participants who were seronegative (n = 26) at baseline demonstrated seroconversion 6 weeks after Dose 2. Among participants who were seropositive at baseline (n = 23), 60.9% had a ≥4-fold rise in antibody titer 6 weeks after Dose 2. Vaccination was generally well tolerated, with no new safety signals identified. Administration of 2 doses of VARIVAX in adults in Russia results in acceptable immune responses with safety data consistent with the licensed product (Clinicaltrials.gov identifier: NCT03843632).

The vaccine coverage and vaccine immunity status and risk factors of non-protective levels of antibodies against vaccines in children with juvenile idiopathic arthritis: cross-sectional Russian tertiary Centre study.

BACKGROUND: Immunosuppressive drugs, incomplete vaccine coverage, immune system dysregulation might be factors of a low level of anti-vaccine antibodies in JIA patients. The study aimed to evaluate vaccine coverage, post-vaccine immunity, and risk factors of non-protective levels of antibodies against measles, mumps, rubella, hepatitis B, and diphtheria in JIA patients. METHODS: A cross-sectional study included 170 children diagnosed with JIA aged 2 to 17 years who received routine vaccinations against measles, rubella, mumps (MMR), diphtheria, and hepatitis B national vaccine schedule. In all patients, the levels of post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B, and diphtheria were measured with ELISA. RESULTS: Protective level of antibodies were 50% against hepatitis B, 52% - diphtheria, 58% - measles, 80% - mumps, 98% rubella. MMR's best coverage had patients with enthesitis-related arthritis-85%, compared to oligoarthritis-70%, polyarthritis-69%, systemic arthritis-63%. Diphtheria coverage was 50, 51, 46, 63%, respectively. Incomplete MMR vaccination had 39% patients, treated with biologics, 22% with methotrexate and 14% with NSAID (p = 0.025), and 61, 46, 36% for diphtheria (p = 0.021). Incomplete vaccination was a risk factor of non-protective level of antibodies against measles (HR = 2.03 [95%CI: 1.02; 4.0], p = 0.042), mumps (HR = 6.25 [95%CI: 2.13; 17.9], p = 0.0008) and diphtheria (HR = 2.39 [95%CI: 1.18; 4.85], p = 0.016) vaccines, as well as JIA category, biologics, corticosteroids and long-term methotrexate treatment for distinct vaccines. One-third part of JIA patients continued vaccination against MMR and diphtheria without serious adverse events and JIA flare. There were no differences between patients who continued MMR vaccination or denied in the means of JIA category and treatment options. Patients, continued diphtheria vaccination rare received methotrexate (p = 0.02), biologics (p = 0.004), but had higher levels of anti-diphtheria antibodies (p = 0.024) compare who omitted vaccination. Methotrexate (OR = 9.5 [95%CI: 1.004; 90.3]) and biologics (OR = 4.4 [95%CI: 1.6; 12.1]) were predictors of omitted diphtheria revaccination. CONCLUSION: Children with JIA may have lower anti-vaccine antibody levels and required routine checks, especially in children with incomplete vaccination, biologics, systemic arthritis, and long-term methotrexate treatment. Revaccination of JIA patients was safe and effective.

Safety and Immunogenicity of Two Doses of a Quadrivalent Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine in Indian and Russian Children Aged 9 to 17 Months.

OBJECTIVE: Evaluation of tolerability, safety and immunogenicity of a two-dose series of a quadrivalent meningococcal polysaccharide diptheria toxoid conjugate (ACYW-D) vaccine in Indian and Russian infants/toddlers. DESIGN: Open-label, single-arm, phase III multi-national trial. STUDY PARTICIPANTS: 300 children aged 9-17 months, previously unvaccinated against meningococcal disease from four sites each in India (n=200) and the Russian Federation (n=100). INTERVENTION: Two 0.5 mL doses of ACYW-D by intramuscular injection, 3-6 months apart. MAIN OUTCOME MEASURES: Meningococcal antibody titers to serogroups A, C, W-135 and Y, determined using a serum bactericidal assay in the presence of human complement before vaccination and 28 days after the second vaccination. Titers ≥1:8 against either/all of the A, C, W-135 or Y were considered sero-protective. RESULTS: After dose 2, 95.7-99.5% and 92.9-99.0% of infants/toddlers achieved seroprotection across the four serogroups in India and the Russian Federation, respectively. No immediate adverse events were reported after any dose of ACYW-D. Solicited reactions were reported in 49.2% of participants, and were mainly of Grade 1 severity, and resolved within three days. Unsolicited adverse events were reported in 19.1% of infants: one event (Grade 3 diarrhea, resolving within one day) was considered related to study vaccine. No non-serious adverse events led to premature withdrawal from the study. Four serious adverse events were reported; none were considered related to study vaccine. No deaths occurred during the study. CONCLUSIONS: A two-dose series of ACYW-D vaccine in Indian and Russian children (9-17 month) was well-tolerated with no safety concerns, and induced robust bactericidal antibody responses against the meningococcal serogroups contained in the vaccine.

Burden of Childhood Rotavirus Disease in the Outpatient Setting of the Russian Federation.

BACKGROUND: This is a prospective, multicentered study conducted in 9 large urban areas in Russia, in order to determine the burden of rotavirus gastroenteritis in children <5 years of age and the genotypes circulating during 1 rotavirus season. METHODS: From November 2012 to May 2013, surveillance was conducted in Moscow, Saint-Petersburg, Vologda, Krasnodar, Krasnoyarsk, Novosibirsk, Yaroslavl, Khanty-Mansiysk and Vladivostok. Children <5 years of age presenting at outpatient clinics with acute gastroenteritis (AGE) of less than 72 hours duration were enrolled in the study. Stool samples were tested for rotavirus and positive samples were P- and G-typed. Clinical symptoms were captured by physicians and parents on Day 1. Symptom severity was analyzed by Vesikari scoring system. The direct expenses of parents caused by AGE were obtained from questionnaires provided to parents by phone. RESULTS: A total of 501 were children enrolled. Stool samples were analyzed for 487 (97%) children, and 151 (31%) of those were rotavirus positive. Rotavirus gastroenteritis was associated with more severe clinical course (Vesikari score 11.4 ± 2.2) versus non-rotavirus gastroenteritis (Vesikari score 9 ± 3). The identified serotypes were G4P[8] 38.9%, G1P[8] 34.2%, G3P[8] 6%, G9P[8] 6%, G2P[4] 2% and G4P[4] 0.7%. The mean overall expenses of parents caused by rotavirus and non-rotavirus gastroenteritis were 143.7 USD and 128.8 USD, respectively. CONCLUSIONS: Rotavirus accounted for 31% of all AGE-related outpatient visits. The major rotavirus genotypes were G1P[8] and G4P[8]. Rotavirus gastroenteritis was associated with significantly more severe clinical symptoms than non-rotavirus gastroenteritis. The average costs of rotavirus cases for parents of children were elevated against the same indications for non-rotavirus. These findings underscore the need for a safe and effective rotavirus vaccine in Russia.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

Streptococcus pneumoniae serotype distribution in children in the Russian Federation before the introduction of pneumococcal conjugate vaccines into the National Immunization Program.

WHO recommends the inclusion of PCVs in childhood vaccination programs world-wide. Many countries including the Russian Federation are currently planning the inclusion of PCVs in their National Immunization Programs and, therefore, data on the pneumococcal serotype distribution is important to estimate the potential disease impact. Here we review eight recent epidemiological studies on the pneumococcal serotype distribution from Russia. Across all studies, serotypes 6B, 14, 19F and 23F were the most prevalent. Interestingly, serotype 3 was relatively common. Serotype 19A was prevalent among AOM, CAP and nasopharyngeal isolates and among antibiotic resistant isolates in all age groups. The differences in serotype coverage between PCV10 and PCV13 were up to 26%. Based on the current data on serotype distribution, a wide use of PCVs in Russia may lead to a significant reduction of the pneumococcal disease burden.