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

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.