Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2
By A. Walls, B. Fiala, A. Schäfer, Samuel P Wrenn, Minh N. Pham, M. Murphy, Longping V. Tse, Laila Shehata, M. O’Connor, Chengbo Chen and 32 more. 2020
428 citations recorded by the source corpus.
A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.
Subfields: Immunology, Infectious Diseases, Computational Biology & Bioinformatics, Medical & Health AI
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Citations in the corpus
- Robust deep learning based protein sequence design using ProteinMPNN (2022, positive): “Thus ProteinMPNN can robustly design sequences that assemble into designed nanoparticles, which have proven useful in several biotechnological applications including structure-based vaccine design (16–18).”
- Broadly applicable and accurate protein design by integrating structure prediction networks and diffusion generative models (2022, positive): “On the other hand, symmetric presentation of viral epitopes in an arrangement that mimics the virus could induce new classes of neutralizing antibodies 37,38 .”
- Title: Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (2020, positive): “In conclusion, we confirmed that multimerization of RBDs on nanoparticles enhances immunogenicity compared with soluble antigen (33, 48) and further showed that homotypic SARS-2 nanoparticle immunization produced IgG responses that bound zoonotic RBDs and neutralized heterologous coronaviruses after”
- Vaccine adjuvants: mechanisms and platforms (2023, background): “The SARS-CoV-2 vaccine based on I53-50 showed 60 SARS-CoV-2 spike receptor binding domains in the highly immunogenic motif, which produced a neutralizing antibody titer 10 times higher than that of the control vaccine.(305) Similarly, a nanoparticle vaccine based on I53-50 that can display 20 respir”