lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

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

24 Pages Posted: 27 Jul 2022

See all articles by Maria Eugenia-Toledo-Romani

Maria Eugenia-Toledo-Romani

Instituto de Medicina Tropical Pedro Kouri

Mayra García Carmenate

Havana Hygiene and Epidemiology Center

Carmen Valenzuela-Silva

Institute of Cybernetics, Mathematics and Physics (ICIMAF)

Waldemar Baldoquín-Rodríguez

Instituto de Medicina Tropical Pedro Kouri

Marisel Martínez-Pérez

Instituto de Medicina Tropical Pedro Kouri

Meiby Rodriguez-González

Finlay Vaccine Institute

Beatriz Paredes-Moreno

Finlay Vaccine Institute

Ivis Mendoza-Hernández

National Coordinating Center for Clinical Trials

Raul González-Mugica

Finlay Vaccine Institute

Oscar Samón-Tabío

“José Antonio Echevarría” Technological University

Pablo Velazco-Villares

UCT Geocuba Research and Consulting

Juan Pablo Bacallao-Castillo

UCT Geocuba Research and Consulting

Ernesto Licea-Martín

Finlay Vaccine Institute

Misladys Rodríguez-Ortega

Instituto de Medicina Tropical Pedro Kouri

Nuris Herrera-Marrero

Instituto de Medicina Tropical Pedro Kouri

Esperanza Caballero-González

Finlay Vaccine Institute

Liudmila Egües-Torres

Havana Hygiene and Epidemiology Center

Reinaldo Duartes-González

Municipal Health Department, Centro Habana

Serguey García-Blanco

Municipal Health Department, La Lisa

Suzette Pérez-Cabrera Pérez-Cabrera

Municipal Health Department, 10 de Octubre

Santos Huete-Ferreira

Municipal Health Department, Habana Vieja

Kirenia Idalmis-Cisnero Idalmis-Cisnero

Municipal Health Department, Cerro

Omayda Fonte-Galindo

Municipal Health Department, Marianao

Dania Melia-Pérez

Municipal Health Department, Plaza Havana

Ivonne Rojas-Remedios

Municipal Health Department, Plaza Havana

Delaram Doroud

Pasteur Institute of Iran

Mohammad Mehdi Gouya

Iran University of Medical Sciences

Alireza Biglari

Pasteur Institute of Iran

Patrick Van der Stuyft Van der Stuyft

Ghent University

Sonsire Fernandez-Castillo

Finlay Vaccine Institute

Yanet Climent-Ruiz

Finlay Vaccine Institute

Yury Valdés-Balbín

Finlay Vaccine Institute

Dagmar García-Rivera

Finlay Vaccine Institute

Vicente Verez-Bencomo

Finlay Vaccine Institute

More...

Abstract

Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralizing IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralizing antibodies.

Methods: From March 8th to September 30th, 2021 we conducted in Havana, Cuba a multicentre randomized, double-blind, placebo-controlled, phase-3 trial evaluating two doses of SOBERANA-02 and a heterologous scheme with one dose SOBERANA-Plus added to it. Participants 19–80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 occurring at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose.

Finding: We included 44·031 participants in a context of Beta VOC predominance, with this variant being gradually replaced by Delta near the trial end. Vaccine efficacy in the heterologous combination was 92·0% (95%CI 80·4–96·7) against symptomatic and 100% against severe COVID-19. Two doses of SOBERANA-02 was 69·7% (95%CI 56·5-78·9) and 74·9% (95%CI 33·7-90·5) efficacious to protect against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe AEs was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient.

Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC dominance and that they constitute an attractive, feasible option for low- and middle-income countries, where besides financial constraints ease of vaccine storage and distribution is of concern.

Trial Registration Details: (Clinical Trials IFV/COR/09 number, RPCEC00000354).

Funding Information: This study received funds from Finlay Vaccine Institute and National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020–20). of Ministry of Science, Technology and the Environment (Contract Project-2020-20) in Cuba.

Declaration of Interests: None to declare.

Ethics Approval Statement: The trial was sponsored by the Finlay Vaccine Institute. A central Research Ethics Committee was appointed ad hoc by the Cuban Ministry of Public Health. . It approved the protocol. and the informed consent forms. In the event of a medical problem requiring unmasking, approval by the principal investigator was planned for. All principles of the Helsinki Declaration and the International Council for Harmonization guidelines were adhered to. Full details on procedures are provided in the protocol. The National Clinical Trials Coordinating Centre (CENCEC) monitored the trial for protocol adherence and observance of Good Clinical Practice, and oversaw data accuracy. An Independent Safety Data Monitoring Board (ISDMB) continuously supervised safety and conducted interim analysis. The ISDMB had access to the case files, confirmed severe cases of COVID-19 illness, and assessed whether any deaths were SARS CoV-2-related.

Keywords: conjugate-vaccine, SARS-COV-2, COVID-19 Vaccine, heterologous scheme, RBD-subunit vaccine, vaccine efficacy

Suggested Citation

Eugenia-Toledo-Romani, Maria and García Carmenate, Mayra and Valenzuela-Silva, Carmen and Baldoquín-Rodríguez, Waldemar and Martínez-Pérez, Marisel and Rodriguez-González, Meiby and Paredes-Moreno, Beatriz and Mendoza-Hernández, Ivis and González-Mugica, Raul and Samón-Tabío, Oscar and Velazco-Villares, Pablo and Bacallao-Castillo, Juan Pablo and Licea-Martín, Ernesto and Rodríguez-Ortega, Misladys and Herrera-Marrero, Nuris and Caballero-González, Esperanza and Egües-Torres, Liudmila and Duartes-González, Reinaldo and García-Blanco, Serguey and Pérez-Cabrera, Suzette Pérez-Cabrera and Huete-Ferreira, Santos and Idalmis-Cisnero, Kirenia Idalmis-Cisnero and Fonte-Galindo, Omayda and Melia-Pérez, Dania and Rojas-Remedios, Ivonne and Doroud, Delaram and Mehdi Gouya, Mohammad and Biglari, Alireza and Van der Stuyft, Patrick Van der Stuyft and Fernandez-Castillo, Sonsire and Climent-Ruiz, Yanet and Valdés-Balbín, Yury and García-Rivera, Dagmar and Verez-Bencomo, Vicente, 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. Available at SSRN: https://ssrn.com/abstract=4174293 or http://dx.doi.org/10.2139/ssrn.4174293

Maria Eugenia-Toledo-Romani

Instituto de Medicina Tropical Pedro Kouri ( email )

Mayra García Carmenate

Havana Hygiene and Epidemiology Center ( email )

Carmen Valenzuela-Silva

Institute of Cybernetics, Mathematics and Physics (ICIMAF)

Waldemar Baldoquín-Rodríguez

Instituto de Medicina Tropical Pedro Kouri ( email )

Marisel Martínez-Pérez

Instituto de Medicina Tropical Pedro Kouri ( email )

Meiby Rodriguez-González

Finlay Vaccine Institute ( email )

Beatriz Paredes-Moreno

Finlay Vaccine Institute ( email )

Ivis Mendoza-Hernández

National Coordinating Center for Clinical Trials ( email )

Raul González-Mugica

Finlay Vaccine Institute ( email )

Oscar Samón-Tabío

“José Antonio Echevarría” Technological University ( email )

Pablo Velazco-Villares

UCT Geocuba Research and Consulting ( email )

Juan Pablo Bacallao-Castillo

UCT Geocuba Research and Consulting ( email )

Ernesto Licea-Martín

Finlay Vaccine Institute ( email )

Misladys Rodríguez-Ortega

Instituto de Medicina Tropical Pedro Kouri ( email )

Nuris Herrera-Marrero

Instituto de Medicina Tropical Pedro Kouri ( email )

Esperanza Caballero-González

Finlay Vaccine Institute ( email )

Liudmila Egües-Torres

Havana Hygiene and Epidemiology Center ( email )

Reinaldo Duartes-González

Municipal Health Department, Centro Habana ( email )

Serguey García-Blanco

Municipal Health Department, La Lisa ( email )

Suzette Pérez-Cabrera Pérez-Cabrera

Municipal Health Department, 10 de Octubre ( email )

Santos Huete-Ferreira

Municipal Health Department, Habana Vieja ( email )

Kirenia Idalmis-Cisnero Idalmis-Cisnero

Municipal Health Department, Cerro ( email )

Omayda Fonte-Galindo

Municipal Health Department, Marianao ( email )

Dania Melia-Pérez

Municipal Health Department, Plaza Havana ( email )

Ivonne Rojas-Remedios

Municipal Health Department, Plaza Havana ( email )

Delaram Doroud

Pasteur Institute of Iran ( email )

Pasteur Institute of Iran
Jomhhoori Street
Tehran, 131694355
Iran

Mohammad Mehdi Gouya

Iran University of Medical Sciences ( email )

Hemmat Hwy
Tehran
Iran

Alireza Biglari

Pasteur Institute of Iran ( email )

Pasteur Institute of Iran
Jomhhoori Street
Tehran, 131694355
Iran

Patrick Van der Stuyft Van der Stuyft

Ghent University ( email )

Coupure Links 653
Gent, 9000
Belgium

Sonsire Fernandez-Castillo

Finlay Vaccine Institute ( email )

Havana
Cuba

Yanet Climent-Ruiz

Finlay Vaccine Institute

Yury Valdés-Balbín

Finlay Vaccine Institute

Dagmar García-Rivera

Finlay Vaccine Institute

Vicente Verez-Bencomo (Contact Author)

Finlay Vaccine Institute

Click here to go to TheLancet.com

Paper statistics

Abstract Views
44
Downloads
15
PlumX Metrics