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

  title={SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies},
  author={Yury Vald{\'e}s-Balb{\'i}n and Darielys Santana-Mederos and Lauren Quintero and Sonsire Fern{\'a}ndez and Laura M Rodr{\'i}guez and Belinda S{\'a}nchez Ram{\'i}rez and Rocmira P{\'e}rez and Claudia Acosta and Yanira M{\'e}ndez and Manuel G. Ricardo and Tays Hern{\'a}ndez and Gretchen Bergado and Franciscary Pi and Annet Valdes and Tania Carmenate and Ubel Ram{\'i}rez and Reinaldo Oliva and Jean Pierre Soubal and Raine Garrido and F{\'e}lix Cardoso and Mario Landys and Humberto Gonz{\'a}lez and Mildrey Fari{\~n}as and Juliet Enriquez and Enrique Noa and Anamary Suarez and Cheng Fang and Luis Ariel Espinosa and Yassel Ramos and Luis Javier Gonz{\'a}lez and Yanet Climent and Gertrudis Rojas and Ernesto Relova-Hern{\'a}ndez and Yanelys Cabrera Infante and Sum Lai Losada and Tammy Boggiano and Eduardo Ojito and Kalet Le{\'o}n Monz{\'o}n and Fabrizio Chiodo and Françoise Paquet and Guang-Wu Chen and Daniel G. Rivera and Dagmar Garc{\'i}a-Rivera and Vicente V{\'e}rez-Bencomo},
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… Expand
Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines
This review summarizes with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Expand
Chemical Conjugation Strategies for the Development of Protein-Based Subunit Nanovaccines
Covalent conjugation strategies for grafting protein or peptide antigens onto other molecules or nanoparticles to obtain subunit nanovaccines are reviewed and the advantages of chemical conjugations in developing these vaccines are discussed. Expand
In-solution buffer-free digestion for the analysis of SARS-CoV-2 RBD proteins allows a full sequence coverage and detection of post-translational modifications in a single ESI-MS spectrum
In this work, several recombinant RBD proteins produced in five expression systems were characterized using a non-conventional protocol known as in-solution buffer-free digestion (BFD), and it is foresee that it can be also helpful to the characterization of mutated RBD. Expand


Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2
The structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice are described and cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic are launched. Expand
A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity
It is shown that a recombinant vaccine that comprises residues 319–545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates as early as 7 or 14 days after the injection of a single vaccine dose. Expand
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction
A blocking assay based on the recombinant receptor-binding domain of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 receptor provides an alternative to conventional antibody neutralization assays requiring live virus. Expand
Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model
A role for potent neutralizing antibodies (nAbs) in prophylaxis, and potentially therapy, of COVID-19 is suggested, as indicated by maintained weight and low lung viral titers in treated animals, and the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. Expand
Structural basis of a shared antibody response to SARS-CoV-2
It is found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein, which is promising for vaccine design. Expand
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
Mapping studies revealed that the SARS-CoV-2 spike protein contained multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as previously undefined non-RBD epitopes, which provide guidance for vaccine design and are promising candidates for treatment and prevention of COVID-19. Expand
Potently neutralizing and protective human antibodies against SARS-CoV-2
An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans. Expand
Is smaller better? Vaccine targeting recombinant receptor-binding domain might hold the key for mass production of effective prophylactics to fight the COVID-19 pandemic
The study highlights the critical role of the immunogenicity of the RBD domain upon SARS-CoV-2 infection and the alternate vaccine designs that could serve as effective prophylactics against the pandemic. Expand
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology
It is found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores, and the immunodominance of the receptor-binding motif will guide the design of COVID-19 vaccines and therapeutics. Expand
First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine
The findings suggest that the NVX-CoV2373 vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis, and was well tolerated and elicited robust immune responses. Expand