Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials

Eugenia-Toledo-Romani, Maria; Verdecia-Sánchez, Leslyhana; Rodríguez-González, Meiby; Rodríguez-Noda, Laura; Valenzuela-Silva, Carmen; Paredes-Moreno, Beatriz; Sánchez-Ramírez, Belinda; Pérez-Nicado, Rocmira; Gonzalez-Mugica, Raul; Hernández-García, Tays; Bergado-Báez, Gretchen; Pi-Estopiñán, Franciscary; Cruz-Sui, Otto; Fraga-Quintero, Anitza; García-Montero, Majela; Palenzuela-Díaz, Ariel; Baró-Román, Gerardo; Mendoza-Hernández, Ivis; Fernández-Castillo, Sonsire; Climent-Ruíz, Yanet; Santana-Mederos, Darielys; Gonzalez, Ubel Ramírez; García-Vega, Yanelda; Pérez-Massón, Beatriz; Guang-Wu-Chen,; Boggiano-Ayo, Tammy; Ojito-Magaz, Eduardo; Rivera, Daniel G.; Valdés-Balbín, Yury; García-Rivera, Dagmar; Vérez-Bencomo, Vicente

doi:10.1016/j.vaccine.2022.05.082

Cited by 31 publications

(42 citation statements)

References 40 publications

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“…10 A third heterologous dose of SOBERANA-Plus after two doses of SOBERANA-02 significantly increased neutralizing anti-RBD IgG titres. 8 These results were confirmed in a phase 2b clinical trial. 11…”

Section: Introductionmentioning

confidence: 70%

“…4 The immunogenicity pattern observed in a phase 1 and 2a trials suggested as the best option two doses of 25-µg SOBERANA-02 followed by a third dose of SOBERANA-Plus. 8 In phase 2b the 4-fold anti-RBD IgG seroconversion rate in 758 volunteers was 76•3 % after two doses and 96•8% after the third heterologous dose, against 7.3% in the placebo group. 11 Neutralizing IgG antibodies were detected against D614G and VOCs Alpha, Beta, Delta and Omicron, and neutralizing antibodies were still present 7-8 months after the third dose.…”

Section: Discussionmentioning

confidence: 96%

“…20,21 Furthermore, due to the T-epitopes from the tetanus toxoid carrier protein, SOBERANA-02 -the first conjugate SARS CoV-2 RBD protein based vaccine-induces T-helper response and long lasting immunity. 8,11 Heterologous combination for priming and booster using protein vaccines are reported by others with excellent results. 22,23 Preclinical results highlighted the stimulation of specific B-and T-memory cells, affinity maturation and a significant and boostable IgG immune response in mice.…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

“…The antigen is the recombinant SARS-CoV-2 RBD (25 μg), chemically conjugated to tetanus toxoid and adsorbed on 500 μg alumina. 4, 8 SOBERANA-Plus antigen is a dimeric RBD (50 μg) adsorbed on 1250 μg alumina. 14, 15 The placebo contained SOBERANA-02 ingredients except the active principle.…”

Section: Methodsmentioning

confidence: 99%

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Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-PLUS: double-blind, randomised, placebo-controlled phase 3 clinical trial

Toledo-Romaní

García-Carmenate²,

Valenzuela-Silva

et al. 2021

Preprint

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BackgroundSOBERANA 02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phase 1 and 2 clinical trials demonstrated its high immunogenicity, promoting neutralizing IgG and specific T-cell response. A third dose, of SOBERANA Plus (RBD-dimer), further increased the specific anti-RBD neutralizing antibodies.MethodsIn a randomized, double-blind, placebo-controlled, phase-3 trial (https://rpcec.sld.cu/trials/RPCEC00000354-En) we randomly assigned 44 031 participants, aged 19–80 years to three groups to receive a) two doses, SOBERANA 02, or b) two doses, SOBERANA 02 and a third dose, SOBERANA Plus, or c) placebo. Study endpoints are vaccine efficacy (VE) evaluated through confirmed symptomatic COVID-19 and safety. During the trial, the SARS CoV-2 isolates in Havana were 74.0 % β, shifting gradually to 100% δ.ResultsTwo doses of SOBERANA 02 protected against symptomatic COVID-19: 43 cases in the two-dose group (14 371) vs. 155 in the placebo group (14 403), VE 71.0%, adjusted (CI 95%, 58.9–79.1). The heterologous three-dose combination increased the protection: 15 cases in the vaccine groups (13 833) vs. 155 in the placebo group (14 303), VE 92.4%, adjusted (CI 95%, 86.9–95.6%). For the two-dose schedule, VE against severe COVID-19 was 63.0% and for death, 59.0%; for the heterologous three-dose schedule, VE was 100% in both cases.ConclusionsThis is the first phase-3 study of a three-dose, heterologous COVID-19 vaccine. Two doses of SOBERANA 02 were safe and attained efficacy of 71.0% in the adult population 19-80 y/o; incorporating SOBERANA Plus increased efficacy from 71.0 % to 92.4%.

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-PLUS: double-blind, randomised, placebo-controlled phase 3 clinical trial

Toledo-Romaní

García-Carmenate²,

Valenzuela-Silva

et al. 2021

Preprint

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Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

et al. 2023

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ImportanceRandomized clinical trials (RCTs) on COVID-19 are increasingly being posted as preprints before publication in a scientific, peer-reviewed journal.ObjectiveTo assess time to journal publication for COVID-19 RCT preprints and to compare differences between pairs of preprints and corresponding journal articles.Evidence ReviewThis systematic review used a meta-epidemiologic approach to conduct a literature search using the World Health Organization COVID-19 database and Embase to identify preprints published between January 1 and December 31, 2021. This review included RCTs with human participants and research questions regarding the treatment or prevention of COVID-19. For each preprint, a literature search was done to locate the corresponding journal article. Two independent reviewers read the full text, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Time to publication was analyzed using a Cox proportional hazards regression model. Differences between preprint and journal article pairs in terms of outcomes, analyses, results, or conclusions were described. Statistical analysis was performed on October 17, 2022.FindingsThis study included 152 preprints. As of October 1, 2022, 119 of 152 preprints (78.3%) had been published in journals. The median time to publication was 186 days (range, 17-407 days). In a multivariable model, larger sample size and low risk of bias were associated with journal publication. With a sample size of less than 200 as the reference, sample sizes of 201 to 1000 and greater than 1000 had hazard ratios (HRs) of 1.23 (95% CI, 0.80-1.91) and 2.19 (95% CI, 1.36-3.53) for publication, respectively. With high risk of bias as the reference, medium-risk articles with some concerns for bias had an HR of 1.77 (95% CI, 1.02-3.09); those with a low risk of bias had an HR of 3.01 (95% CI, 1.71-5.30). Of the 119 published preprints, there were differences in terms of outcomes, analyses, results, or conclusions in 65 studies (54.6%). The main conclusion in the preprint contradicted the conclusion in the journal article for 2 studies (1.7%).Conclusions and RelevanceThese findings suggest that there is a substantial time lag from preprint posting to journal publication. Preprints with smaller sample sizes and high risk of bias were less likely to be published. Finally, although differences in terms of outcomes, analyses, results, or conclusions were observed for preprint and journal article pairs in most studies, the main conclusion remained consistent for the majority of studies.

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Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine

et al. 2023

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ImportanceThe protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown.ObjectiveTo evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults.Design, Setting, and ParticipantsA multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021.InterventionsIn cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection.Main Outcomes and MeasuresThe primary outcome was polymerase chain reaction–confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed.ResultsIn cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths.Conclusions and RelevanceIn this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19–related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price.Trial Registrationisrctn.org Identifier: IRCT20210303050558N1

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Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials

Cited by 31 publications

References 40 publications

Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-PLUS: double-blind, randomised, placebo-controlled phase 3 clinical trial

Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-PLUS: double-blind, randomised, placebo-controlled phase 3 clinical trial

Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine

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