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-Nicado; 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 León; Fabrizio Chiodo; Françoise Paquet; Guang-Wu Chen; Daniel G. Rivera; Dagmar Garcia-Rivera; Vicente Verez Bencomo

doi:10.1021/acschembio.1c00272

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-Nicado, 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 CardosoMario 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 León, Fabrizio Chiodo, Françoise Paquet, Guang-Wu Chen, Daniel G. Rivera, Dagmar Garcia-Rivera, Vicente Verez Bencomo

Molecular cell biology and Immunology

Research output: Contribution to journal › Article › Academic › peer-review

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 elicit 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 immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.

Original language	English
Pages (from-to)	1223-1233
Number of pages	11
Journal	Acs chemical biology
Volume	16
Issue number	7
Early online date	2021
DOIs	https://doi.org/10.1021/acschembio.1c00272
Publication status	Published - 16 Jul 2021

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10.1021/acschembio.1c00272

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Valdes-Balbin, Y., Santana-Mederos, D., Quintero, L., Fernández, S., Rodriguez, L., Sanchez Ramirez, B., Perez-Nicado, R., Acosta, C., Méndez, Y., Ricardo, M. G., Hernandez, T., Bergado, G., Pi, F., Valdes, A., Carmenate, T., Ramirez, U., Oliva, R., Soubal, J-P., Garrido, R., ... Verez Bencomo, V. (2021). SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies. Acs chemical biology, 16(7), 1223-1233. https://doi.org/10.1021/acschembio.1c00272

Valdes-Balbin, Yury ; Santana-Mederos, Darielys ; Quintero, Lauren ; Fernández, Sonsire ; Rodriguez, Laura ; Sanchez Ramirez, Belinda ; Perez-Nicado, Rocmira ; Acosta, Claudia ; Méndez, Yanira ; Ricardo, Manuel G. ; Hernandez, Tays ; Bergado, Gretchen ; Pi, Franciscary ; Valdes, Annet ; Carmenate, Tania ; Ramirez, Ubel ; Oliva, Reinaldo ; Soubal, Jean-Pierre ; Garrido, Raine ; Cardoso, Felix ; Landys, Mario ; Gonzalez, Humberto ; Farinas, Mildrey ; Enriquez, Juliet ; Noa, Enrique ; Suarez, Anamary ; Fang, Cheng ; Espinosa, Luis A. ; Ramos, Yassel ; González, Luis Javier ; Climent, Yanet ; Rojas, Gertrudis ; Relova-Hernández, Ernesto ; Cabrera Infante, Yanelys ; Losada, Sum Lai ; Boggiano, Tammy ; Ojito, Eduardo ; León, Kalet ; Chiodo, Fabrizio ; Paquet, Françoise ; Chen, Guang-Wu ; Rivera, Daniel G. ; Garcia-Rivera, Dagmar ; Verez Bencomo, Vicente. / SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies. In: Acs chemical biology. 2021 ; Vol. 16, No. 7. pp. 1223-1233.

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title = "SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies",

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 elicit 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 immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.",

author = "Yury Valdes-Balbin and Darielys Santana-Mederos and Lauren Quintero and Sonsire Fern{\'a}ndez and Laura Rodriguez and {Sanchez Ramirez}, Belinda and Rocmira Perez-Nicado and Claudia Acosta and Yanira M{\'e}ndez and Ricardo, {Manuel G.} and Tays Hernandez and Gretchen Bergado and Franciscary Pi and Annet Valdes and Tania Carmenate and Ubel Ramirez and Reinaldo Oliva and Jean-Pierre Soubal and Raine Garrido and Felix Cardoso and Mario Landys and Humberto Gonzalez and Mildrey Farinas and Juliet Enriquez and Enrique Noa and Anamary Suarez and Cheng Fang and Espinosa, {Luis A.} and Yassel Ramos and Gonz{\'a}lez, {Luis Javier} and Yanet Climent and Gertrudis Rojas and Ernesto Relova-Hern{\'a}ndez and {Cabrera Infante}, Yanelys and Losada, {Sum Lai} and Tammy Boggiano and Eduardo Ojito and Kalet Le{\'o}n and Fabrizio Chiodo and Fran{\c c}oise Paquet and Guang-Wu Chen and Rivera, {Daniel G.} and Dagmar Garcia-Rivera and {Verez Bencomo}, Vicente",

note = "Funding Information: We thank R. P{\'e}rez, L. Herrera, A. Lage, and E. Martinez (BioCubaFarma) for advice and support to the project; L. Castellanos for scientific advice and corrections; G. Reed for editing the English version; and E. Ramos for the figures{\textquoteright} design. We are grateful to Fondo de Ciencia e Innovacion (FONCI, CITMA, Cuba) for financial support (Project-2020-20) and to the Leibniz Institute of Plant Biochemistry, Germany, for support in structural characterization. Publisher Copyright: {\textcopyright} Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jul,

day = "16",

doi = "10.1021/acschembio.1c00272",

language = "English",

volume = "16",

pages = "1223--1233",

journal = "Acs chemical biology",

issn = "1554-8929",

publisher = "American Chemical Society",

number = "7",

}

Valdes-Balbin, Y, Santana-Mederos, D, Quintero, L, Fernández, S, Rodriguez, L, Sanchez Ramirez, B, Perez-Nicado, R, Acosta, C, Méndez, Y, Ricardo, MG, Hernandez, T, Bergado, G, Pi, F, Valdes, A, Carmenate, T, Ramirez, U, Oliva, R, Soubal, J-P, Garrido, R, Cardoso, F, Landys, M, Gonzalez, H, Farinas, M, Enriquez, J, Noa, E, Suarez, A, Fang, C, Espinosa, LA, Ramos, Y, González, LJ, Climent, Y, Rojas, G, Relova-Hernández, E, Cabrera Infante, Y, Losada, SL, Boggiano, T, Ojito, E, León, K, Chiodo, F, Paquet, F, Chen, G-W, Rivera, DG, Garcia-Rivera, D & Verez Bencomo, V 2021, 'SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies', Acs chemical biology, vol. 16, no. 7, pp. 1223-1233. https://doi.org/10.1021/acschembio.1c00272

SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies. / Valdes-Balbin, Yury; Santana-Mederos, Darielys; Quintero, Lauren; Fernández, Sonsire; Rodriguez, Laura; Sanchez Ramirez, Belinda; Perez-Nicado, Rocmira; Acosta, Claudia; Méndez, Yanira; Ricardo, Manuel G.; Hernandez, Tays; Bergado, Gretchen; Pi, Franciscary; Valdes, Annet; Carmenate, Tania; Ramirez, Ubel; Oliva, Reinaldo; Soubal, Jean-Pierre; Garrido, Raine; Cardoso, Felix; Landys, Mario; Gonzalez, Humberto; Farinas, Mildrey; Enriquez, Juliet; Noa, Enrique; Suarez, Anamary; Fang, Cheng; Espinosa, Luis A.; Ramos, Yassel; González, Luis Javier; Climent, Yanet; Rojas, Gertrudis; Relova-Hernández, Ernesto; Cabrera Infante, Yanelys; Losada, Sum Lai; Boggiano, Tammy; Ojito, Eduardo; León, Kalet; Chiodo, Fabrizio; Paquet, Françoise; Chen, Guang-Wu; Rivera, Daniel G.; Garcia-Rivera, Dagmar; Verez Bencomo, Vicente.

In: Acs chemical biology, Vol. 16, No. 7, 16.07.2021, p. 1223-1233.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies

AU - Valdes-Balbin, Yury

AU - Santana-Mederos, Darielys

AU - Quintero, Lauren

AU - Fernández, Sonsire

AU - Rodriguez, Laura

AU - Sanchez Ramirez, Belinda

AU - Perez-Nicado, Rocmira

AU - Acosta, Claudia

AU - Méndez, Yanira

AU - Ricardo, Manuel G.

AU - Hernandez, Tays

AU - Bergado, Gretchen

AU - Pi, Franciscary

AU - Valdes, Annet

AU - Carmenate, Tania

AU - Ramirez, Ubel

AU - Oliva, Reinaldo

AU - Soubal, Jean-Pierre

AU - Garrido, Raine

AU - Cardoso, Felix

AU - Landys, Mario

AU - Gonzalez, Humberto

AU - Farinas, Mildrey

AU - Enriquez, Juliet

AU - Noa, Enrique

AU - Suarez, Anamary

AU - Fang, Cheng

AU - Espinosa, Luis A.

AU - Ramos, Yassel

AU - González, Luis Javier

AU - Climent, Yanet

AU - Rojas, Gertrudis

AU - Relova-Hernández, Ernesto

AU - Cabrera Infante, Yanelys

AU - Losada, Sum Lai

AU - Boggiano, Tammy

AU - Ojito, Eduardo

AU - León, Kalet

AU - Chiodo, Fabrizio

AU - Paquet, Françoise

AU - Chen, Guang-Wu

AU - Rivera, Daniel G.

AU - Garcia-Rivera, Dagmar

AU - Verez Bencomo, Vicente

N1 - Funding Information: We thank R. Pérez, L. Herrera, A. Lage, and E. Martinez (BioCubaFarma) for advice and support to the project; L. Castellanos for scientific advice and corrections; G. Reed for editing the English version; and E. Ramos for the figures’ design. We are grateful to Fondo de Ciencia e Innovacion (FONCI, CITMA, Cuba) for financial support (Project-2020-20) and to the Leibniz Institute of Plant Biochemistry, Germany, for support in structural characterization. Publisher Copyright: © Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7/16

Y1 - 2021/7/16

N2 - 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 elicit 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 immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.

AB - 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 elicit 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 immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.

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U2 - 10.1021/acschembio.1c00272

DO - 10.1021/acschembio.1c00272

M3 - Article

C2 - 34219448

VL - 16

SP - 1223

EP - 1233

JO - Acs chemical biology

JF - Acs chemical biology

SN - 1554-8929

IS - 7

ER -