Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults

Toledo-Romaní, María Eugenia; García-Carmenate, Mayra; Verdecia-Sánchez, Leslyhana; Pérez-Rodríguez, Suzel; Rodriguez-Gonzalez, Meybis; Valenzuela-Silva, Carmen; Paredes-Moreno, Beatriz; Sánchez-Ramírez, Belinda; Gonzalez-Mugica, Raul; Hernández-García, Tays; Orosa-Vázquez, Ivette; Díaz-Hernández, Marianniz; Pérez-Guevara, María Teresa; Enríquez-Puertas, Juliet; Noa-Romero, Enrique; Palenzuela-Díaz, Ariel; Baró-Román, Gerardo; Mendoza-Hernández, Ivis; Y, Muñoz; Gómez-Maceo, Yanet; Santos-Vega, Bertha Leysi; Fernández-Castillo, Sonsire; Climent-Ruíz, Yanet; Rodríguez-Noda, Laura; Santana-Mederos, Darielys; García-Vega, Yanelda; Chen, Guang-Wu; Doroud, Delaram; Biglari, Alireza; Boggiano-Ayo, Tammy; Valdés-Balbín, Yury; Rivera, Daniel G.; García-Rivera, Dagmar; Vérez-Bencomo, Vicente; Cubas-Curbelo, Mailin; Rodríguez-Castillo, Pedro Gabriel; Acevedo-Martínez, Yosmel; Estoque-Cabrera, Solangel; Ávila-Cabreja, José Alejandro; Alfaro-Guzmán, Ainadis; Zulueta-Pérez, Lilian; Espino-Rojas, Niurka Tamara; Medinas-Santos, Gloria Margarita; Sarda-Rodriguez, Ileana Luisa; Acosta-Martinez, Mario Alejandro; Reyes-Matienzo, Radamet; Coviella-Artime, José Manuel; Morffi-Cinta, Irania; Martínez-Pérez, Marisel; Valera-Fernández, Rodrigo; Garcés-Hechavarría, Aniurka; Martínez-Bedoya, Dayle; Garrido-Arteaga, Raine; Cardoso-SanJorge, Félix; Ramírez-Gonzalez, Ubel; Quintero-Moreno, Lauren; Ontivero-Pino, Ivis; Martínez-Rivera, Roselyn; Guillén-Obregón, Berta; Lora-García, Janet; Medina-Nápoles, Maite; Espi-Ávila, Jennifer; Fontanies-Fernández, Marcos; Domínguez-Pentón, Yeney Regla; Bergado-Báez, Gretchen; Pi-Estopiñán, Franciscary; Ojito-Magaz, Eduardo; Rodríguez, Misladys; Cruz-Sui, Otto; García-Montero, Majela; Dubed-Echevarría, Marta; García-López, Elena; Galano-Frutos, Evelyn; Perez-Perez, Alina; Morales-Ruano, Susana; Brito-Pascual, Idalmis; Amoroto, Maité; Arteaga-García, Amaylid

doi:10.1016/j.medj.2022.08.001

Cited by 23 publications

(24 citation statements)

References 34 publications

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“…2 The encouraging safety profile observed during the phase 2 SOBERANA clinical trial was confirmed in this phase 3 study. 8,11 Pain at the injection site was not uncommon, akin to what has been observed for other subunit protein and mRNA COVID 19 vaccines, 23 but mostly mild, while rates of other local reactions were low. Fever and general discomfort were rather uncommon and generally mild, as were other systemic reactions.…”

Section: Discussionmentioning

confidence: 79%

“…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. 11 The results of the present trial permit to conclude that this leads to improved clinical efficacy of the 3-dose scheme.…”

Section: Discussionmentioning

confidence: 95%

“…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. 11 The results of the present trial permit to conclude that this leads to improved clinical efficacy of the 3-dose scheme.…”

Section: Discussionmentioning

confidence: 95%

“…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: 98%

Section: Discussionmentioning

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: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

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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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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The Assessment of Anti–SARS‐CoV‐2 Antibodies in Different Vaccine Platforms: A Systematic Review and Meta‐Analysis of COVID‐19 Vaccine Clinical Trial Studies

Mirzakhani,

Bayat,

Dashti

et al. 2024

Reviews in Medical Virology

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Background and ObjectiveThe COVID‐19 pandemic spread rapidly throughout the world and caused millions of deaths globally. Several vaccines have been developed to control the COVID‐19 pandemic and reduce the burden it placed on public health. This study aimed to assess the efficacy of different vaccine platforms in inducing potent antibody responses. Moreover, the seroconversion rate and common side effects of vaccine platforms were evaluated.MethodsThis meta‐analysis included clinical trials of COVID‐19 vaccines that met the eligibility criteria. Electronic databases (including PubMed, Scopus, and Web of Science) and Google Scholar search engine were searched for eligible studies. Regarding the methodological heterogeneity between the included studies, we selected a random‐effects model. The geometric mean ratio (GMR) was chosen as the effect size for this meta‐analysis.ResultsOf the 1838 records identified through screening and after removing duplicate records, the full texts of 1076 records were assessed for eligibility. After the full‐text assessment, 56 records were eligible and included in the study. Overall, vaccinated participants had a 150.8‐fold increased rate of anti‐spike IgG titres compared with the placebo group (GMR = 150.8; 95% CI, 95.9–237.1; I2 = 100%). Moreover, vaccinated participants had a 37.3‐fold increased rate of neutralising antibody titres compared with the placebo group (GMR = 37.3; 95% CI, 28.5–48.7; I2 = 99%). The mRNA platform showed a higher rate of anti‐spike IgG (GMR = 1263.5; 95% CI, 431.1–3702.8; I2 = 99%), while neutralising antibody titres were higher in the subunit platform (GMR = 53.4; 95% CI, 32.8–87.1; I2 = 99%) than in other platforms. Different vaccine platforms showed different rates of both anti‐spike IgG and neutralising antibody titres with interesting results. The seroconversion rate of anti‐spike IgG and neutralising antibody titres was more than 98% in the vaccinated participants.ConclusionInactivated and subunit vaccines produced a high percentage of neutralising antibodies and had a low common adverse reaction rate compared to other platforms. In this regard, subunit and inactivated vaccines can still be used as the main vaccine platforms for effectively controlling infections with high transmission rates.

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Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults

Cited by 23 publications

References 34 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

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

The Assessment of Anti–SARS‐CoV‐2 Antibodies in Different Vaccine Platforms: A Systematic Review and Meta‐Analysis of COVID‐19 Vaccine Clinical Trial Studies

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