Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life:A phase III, double-blind, randomized study

BACKGROUND: A new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference. METHODS: In this phase III, double-blind, multi-center study, healthy 12-23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Varand#8201;+and#8201;HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever andgt;and#8201;39.0and#8201;and#176;C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever andgt;and#8201;39.0and#8201;and#176;C was and#8804;5% (Var-HSA group minus Varand#8201;+and#8201;HSA group). Safety, reactogenicity and immune responses were evaluated. RESULTS: Six hundred fifteen children in the Var-HSA group and 616 in the Varand#8201;+and#8201;HSA group received and#8805;1 vaccination. Fever andgt;and#8201;39.0and#8201;and#176;C was reported in 3.9 and 5.2% of participants in the Var-HSA and Varand#8201;+and#8201;HSA groups, with a between-group difference of -and#8201;1.29 (95% confidence interval: -and#8201;3.72-1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Varand#8201;+and#8201;HSA group, during 43and#8201;days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Varand#8201;+and#8201;HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations and#8805;50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups. CONCLUSIONS: The varicella vaccine formulated without HSA did not induce higher rates of fever during the 15and#8201;day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers. TRIAL REGISTRATION:NCT02570126 , registered on 5 October 2015 (www.clinicaltrials.gov).</p

Intervenção física e psicológica com idosos hipertensos: relato de experiência

Introdução: Programas de “envelhecimento ativo” têm sido incentivados pela Organização Mundial de Saúde, desde a publicação do Marco Político de Envelhecimento Ativo (WHO, 2002), visando a contribuir para a saúde e a participação social, econômica, política e cultural da população idosa. Objetivo: Apresentar os resultados de uma intervenção física e psicológica realizada com três grupos de idosos hipertensos, visando à promoção de qualidade de vida dos participantes. Métodos: As atividades foram desenvolvidas durante quatro meses e foram conduzidas por estudantes dos cursos de graduação em Psicologia e Educação Física de uma universidade pública de Minas Gerais. A intervenção física contou com exercícios aeróbicos e anaeróbicos visando à promoção de autonomia; já a intervenção psicológica consistiu de oficinas de grupos operativos para discussão sobre a hipertensão arterial e com atividades que buscavam melhorar a autoestima, o autoconhecimento e a qualidade de vida dos participantes. Resultados: Os resultados foram avaliados qualitativamente e também por meio do instrumento WHOQOL-bref. Verificou-se influência positiva da articulação entre atividades físicas (que auxiliam no fortalecimento dos músculos e na diminuição nos níveis de repouso da pressão arterial) e oficinas grupais que contribuem para a criação de vínculos, o compartilhamento de questões familiares e a experiência de ouvir e se sentir ouvido. Conclusão: As atividades desenvolvidas indicaram melhorias na qualidade de vida dos participantes e podem contribuir para fundamentar possíveis intervenções com esse público em outros contextos, como nos serviços de atenção primária à saúde

Two-year antibody persistence in children vaccinated at 12–15 months with a measles-mumps-rubella virus vaccine without human serum albumin

One combined measles-mumps-rubella (MMR) vaccine without Human Serum Albumin (HSA) is currently licensed in the USA (M-M-R II; Merck, USA) and another has been developed (Priorix™ [MMR-RIT, GSK, Belgium]). In this follow-up study, children from USA or Puerto Rico, who had received one dose of M-M-R II or MMR-RIT at 12–15 months of age in the primary study (NCT00861744), were followed-up for 2 y post-vaccination. Anti-measles and anti-rubella antibodies were measured using Enzyme-Linked Immunosorbent Assay (ELISA), and anti-mumps antibodies using ELISA and plaque reduction neutralization (PRN) assays. Serious adverse events (SAEs) were recorded during the entire follow-up. The according-to-protocol (ATP) persistence cohort included 752 children (M-M-R II = 186, MMR-RIT = 566), who received primary vaccination at a mean age of 12.3 ( ± 0.67) months. 104 children were revaccinated with MMR-containing vaccines; therefore, serology results for timepoints after revaccination were excluded from the analysis. Seropositivity for measles (Year 1≥ 98.3%; Year 2≥ 99.4%) and rubella (Year 1≥ 98.9%; Year 2 = 100%) remained as high at Year 2 as at Day 42. Similarly, seropositivity for mumps determined by ELISA (Year 1≥ 90.1%; Year 2≥ 94.1%) and PRN assays (Year 1≥ 87.5%; Year 2≥ 91.7%) persisted. Thirty-three SAEs were recorded in 23 children; 2 SAEs (inguinal adenitis and idiopathic thrombocytopenic purpura) and one SAE (febrile convulsion) were considered as potentially related to MMR-RIT and M-M-R II, respectively. This study showed that antibodies against measles, mumps and rubella persisted for up to 2 y post-vaccination with either MMR vaccine in children aged 12–15 months, and that both vaccines were well-tolerated during the follow-up period

Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life: a phase III, double-blind, randomized study

Background: a new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference. Methods: in this phase III, double-blind, multi-center study, healthy 12–23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever &gt; 39.0 °C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever &gt; 39.0 °C was ≤5% (Var-HSA group minus Var + HSA group). Safety, reactogenicity and immune responses were evaluated. Results: six hundred fifteen children in the Var-HSA group and 616 in the Var + HSA group received ≥1 vaccination. Fever &gt; 39.0 °C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of − 1.29 (95% confidence interval: − 3.72–1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations ≥50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups. Conclusions: the varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers

Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12–17 year-old adolescents

We previously demonstrated the efficacy of the COVID-19 vaccine candidate, SCB-2019, in adults in the SPECTRA phase 2/3 efficacy study. We extended the study to include 1278 healthy 12–17-year-old adolescents in Belgium, Colombia, and the Philippines who received either two doses of SCB-2019 or placebo 21 days apart, to assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 and variants of concern, and safety and reactogenicity as solicited and unsolicited adverse events with a comparator group of young adults (18–25 years). In participants with no evidence of prior SARS-CoV-2 infection SCB-2019 immunogenicity in adolescents was non-inferior to that in young adults; respective geometric mean neutralizing titers (GMT) against prototype SARS-CoV-2 14 days after the second vaccination were 271 IU/mL (95% CI: 211–348) and 144 IU/mL (116–178). Most adolescents (1077, 84.3%) had serologic evidence of prior SAR-CoV-2 exposure at baseline; in these seropositive adolescents neutralizing GMTs increased from 173 IU/mL (135–122) to 982 IU/mL (881–1094) after the second dose. Neutralizing titers against Delta and Omicron BA SARS-CoV-2 variants were also increased, most notably in those with prior exposure. SCB-2019 vaccine was well tolerated with generally mild or moderate, transient solicited and unsolicited adverse events that were comparable in adolescent vaccine and placebo groups except for injection site pain – reported after 20% of SCB-2019 and 7.3% of placebo injections. SCB-2019 vaccine was highly immunogenic against SARS-CoV-2 prototype and variants in adolescents, especially in those with evidence of prior exposure, with comparable immunogenicity to young adults. Clinical trial registration: EudraCT 2020–004272–17; ClinicalTrials.gov NCT04672395

Immunogenicity of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in SARS-CoV-2-naïve and exposed individuals in a phase 2/3, double-blind, randomized study

Background: We evaluated immunogenicity of SCB-2019, a subunit vaccine candidate containing a prefusion trimeric form of the SARS-CoV-2 spike (S)-protein adjuvanted with CpG-1018/alum.Methods: The phase 2/3, double-blind, randomized SPECTRA trial was conducted in five countries in participants aged 18 years, either SARS-CoV-2-naïve or previously exposed. Participants were randomly assigned to receive two doses of SCB-2019 or placebo administered intramuscularly 21 days apart. In the phase 2 part of the study, on days 1, 22, and 36, neutralizing antibodies were measured by pseudovirus and wild-type virus neutralization assays to SARS-CoV-2 prototype and variants, and ACE2-receptor-binding antibodies and SCB-2019–binding antibodies were measured by ELISA. Cell-mediatedimmunity was measured by intracellular cytokine staining via flow cytometry.Results: 1601 individuals were enrolled between 24 March and 13 September 2021 and received at least one vaccine dose. Immunogenicity analysis was conducted in a phase 2 subset of 691 participants, including 428 SARS-CoV-2-naïve (381 vaccine and 47 placebo recipients) and 263 SARS-CoV-2-exposed (235 vaccine and 28 placebo recipients). In SARS-CoV-2-naïve participants, GMTs of neutralizing antibodies against prototype virus increased 2 weeks post-second dose (day 36) compared to baseline (224 vs 12.7 IU/mL). Seroconversion rate was 82.5 %. In SARS-CoV-2-exposed participants, one SCB-2019 dose increased GMT of neutralizing antibodies by 48.3-fold (1276.1 IU/mL on day 22) compared to baseline.Seroconversion rate was 92.4 %. Increase was marginal post-second dose. SCB-2019 also showed crossneutralization capability against nine variants, including Omicron, in SARS-CoV-2-exposed participants at day 36. SCB-2019 stimulated Th1-biased cell-mediated immunity to the S-protein in both naïve and exposed participants. The vaccine was well tolerated, no safety concerns were raised from the study.Conclusions: A single dose of SCB-2019 was immunogenic in SARS-CoV-2-exposed individuals, whereas two doses were required to induce immune response in SARS-CoV-2-naïve individuals. SCB-2019 elicitedinfo:eu-repo/semantics/publishe

Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS: This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS: 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION: Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations