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SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies

View ORCID ProfileYury Valdes-Balbin, Darielys Santana-Mederos, Lauren Quintero, Sonsire Fernández, Laura Rodriguez, Belinda Sanchez Ramirez, Rocmira Perez, Claudia Acosta, Yanira Méndez, Manuel G. Ricardo, Tays Hernandez, Gretchen Bergado, Franciscary Pi, Annet Valdes, Tania Carmenate, Ubel Ramirez, Reinaldo Oliva, Jean-Pierre Soubal, Raine Garrido, Felix Cardoso, Mario Landys, Humberto Gonzalez, Mildrey Farinas, Juliet Enriquez, Enrique Noa, Anamary Suarez, Cheng Fang, Luis A. Espinosa, Yassel Ramos, Luis Javier González, Yanet Climent, Gertrudis Rojas, Ernesto Relova-Hernández, Yanelys Cabrera Infante, Sum Lai Losada, Tammy Boggiano, Eduardo Ojito, Kalet Leon Monzon, Fabrizio Chiodo, Françoise Paquet, Guang-Wu Chen, View ORCID ProfileDaniel G. Rivera, View ORCID ProfileDagmar Garcia-Rivera, View ORCID ProfileVicente Verez-Bencomo
doi: https://doi.org/10.1101/2021.02.08.430146
Yury Valdes-Balbin
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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  • ORCID record for Yury Valdes-Balbin
  • For correspondence: yvbalbin@finlay.edu.cu dagarcia@finlay.edu.cu vicente.verez@finlay.edu.cu
Darielys Santana-Mederos
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Lauren Quintero
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Sonsire Fernández
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Laura Rodriguez
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Belinda Sanchez Ramirez
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Rocmira Perez
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Claudia Acosta
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Yanira Méndez
3Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Cuba
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Manuel G. Ricardo
3Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Cuba
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Tays Hernandez
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Gretchen Bergado
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Franciscary Pi
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Annet Valdes
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Tania Carmenate
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Ubel Ramirez
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Reinaldo Oliva
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Jean-Pierre Soubal
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Raine Garrido
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Felix Cardoso
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Mario Landys
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Humberto Gonzalez
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Mildrey Farinas
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Juliet Enriquez
4National Civil Defense Research Laboratory, Cuba
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Enrique Noa
4National Civil Defense Research Laboratory, Cuba
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Anamary Suarez
4National Civil Defense Research Laboratory, Cuba
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Cheng Fang
5Shanghai Fenglin Glycodrug Promotion Center, Shanghai 200032, China
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Luis A. Espinosa
6Center for Genetic Engineering and Biotechnology, Ave 31 e/158 y 190, Playa, Havana, Cuba
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Yassel Ramos
6Center for Genetic Engineering and Biotechnology, Ave 31 e/158 y 190, Playa, Havana, Cuba
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Luis Javier González
6Center for Genetic Engineering and Biotechnology, Ave 31 e/158 y 190, Playa, Havana, Cuba
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Yanet Climent
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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Gertrudis Rojas
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Ernesto Relova-Hernández
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Yanelys Cabrera Infante
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Sum Lai Losada
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Tammy Boggiano
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Eduardo Ojito
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Kalet Leon Monzon
2Center of Molecular Immunology, P.O. Box 16040, 216 St. Havana, Cuba
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Fabrizio Chiodo
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
7Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands and Institute of Biomolecular Chemistry, National Research Council (CNR), Pozzuoli, Napoli, Italy
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Françoise Paquet
8Centre de Biophysique Moléculaire, CNRS UPR 4301, rue Charles Sadron, F-45071, Orléans, Cedex 2, France
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Guang-Wu Chen
9Chengdu Olisynn Biotech. Co. Ltd., and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
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Daniel G. Rivera
3Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Cuba
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Dagmar Garcia-Rivera
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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  • ORCID record for Dagmar Garcia-Rivera
  • For correspondence: yvbalbin@finlay.edu.cu dagarcia@finlay.edu.cu vicente.verez@finlay.edu.cu
Vicente Verez-Bencomo
1Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba
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  • For correspondence: yvbalbin@finlay.edu.cu dagarcia@finlay.edu.cu vicente.verez@finlay.edu.cu
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Abstract

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to use neutralizing antibodies to block viral sites binding to the host’s cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of the immunization and correlates well with viral neutralization. Here we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid induce a potent immune response in laboratory animals. Some advantages of the immunization with the viral antigen coupled to tetanus toxoid have become evident such as predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. This paper demonstrates that subunit conjugate vaccines can be an alternative for COVID-19, paving the way for other viral conjugate vaccines based on the use of small viral proteins involved in the infection process.

Competing Interest Statement

Y.V.B., D.S.M, S.F., M.R., L.R., U.R., D.G.R., T.B., E.O., D.G.R., D.G.R., and V.V.B are co-inventor on provisional SARS-CoV-2 vaccine patents (Cu 2020-69).

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 02, 2021.
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SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies
Yury Valdes-Balbin, Darielys Santana-Mederos, Lauren Quintero, Sonsire Fernández, Laura Rodriguez, Belinda Sanchez Ramirez, Rocmira Perez, Claudia Acosta, Yanira Méndez, Manuel G. Ricardo, Tays Hernandez, Gretchen Bergado, Franciscary Pi, Annet Valdes, Tania Carmenate, Ubel Ramirez, Reinaldo Oliva, Jean-Pierre Soubal, Raine Garrido, Felix Cardoso, Mario Landys, Humberto Gonzalez, Mildrey Farinas, Juliet Enriquez, Enrique Noa, Anamary Suarez, Cheng Fang, Luis A. Espinosa, Yassel Ramos, Luis Javier González, Yanet Climent, Gertrudis Rojas, Ernesto Relova-Hernández, Yanelys Cabrera Infante, Sum Lai Losada, Tammy Boggiano, Eduardo Ojito, Kalet Leon Monzon, Fabrizio Chiodo, Françoise Paquet, Guang-Wu Chen, Daniel G. Rivera, Dagmar Garcia-Rivera, Vicente Verez-Bencomo
bioRxiv 2021.02.08.430146; doi: https://doi.org/10.1101/2021.02.08.430146
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SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies
Yury Valdes-Balbin, Darielys Santana-Mederos, Lauren Quintero, Sonsire Fernández, Laura Rodriguez, Belinda Sanchez Ramirez, Rocmira Perez, Claudia Acosta, Yanira Méndez, Manuel G. Ricardo, Tays Hernandez, Gretchen Bergado, Franciscary Pi, Annet Valdes, Tania Carmenate, Ubel Ramirez, Reinaldo Oliva, Jean-Pierre Soubal, Raine Garrido, Felix Cardoso, Mario Landys, Humberto Gonzalez, Mildrey Farinas, Juliet Enriquez, Enrique Noa, Anamary Suarez, Cheng Fang, Luis A. Espinosa, Yassel Ramos, Luis Javier González, Yanet Climent, Gertrudis Rojas, Ernesto Relova-Hernández, Yanelys Cabrera Infante, Sum Lai Losada, Tammy Boggiano, Eduardo Ojito, Kalet Leon Monzon, Fabrizio Chiodo, Françoise Paquet, Guang-Wu Chen, Daniel G. Rivera, Dagmar Garcia-Rivera, Vicente Verez-Bencomo
bioRxiv 2021.02.08.430146; doi: https://doi.org/10.1101/2021.02.08.430146

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