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Conjugated Proteins02:50

Conjugated Proteins

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Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
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Engineering a SARS-CoV-2 Vaccine Targeting the Receptor-Binding Domain Cryptic-Face via Immunofocusing.

Theodora U J Bruun1,2, Jonathan Do1,2, Payton A-B Weidenbacher1,3

  • 1Sarafan ChEM-H, Stanford University, Stanford, California 94305, United States.

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This study developed a new vaccine strategy, PMD-RBD, to elicit broadly neutralizing antibodies against SARS-CoV-2 and related viruses. This approach successfully focused immune responses, enhancing protection against diverse sarbecoviruses.

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Area of Science:

  • Virology
  • Immunology
  • Vaccine Development

Background:

  • The SARS-CoV-2 spike protein's receptor-binding domain (RBD) is a key target for neutralizing antibodies.
  • Antibodies targeting the cryptic face of the RBD show broad neutralization across sarbecoviruses but are rarely induced.
  • Developing immunogens that focus antibody responses on this cryptic epitope is crucial for effective vaccines.

Purpose of the Study:

  • To engineer novel receptor-binding domain (RBD) immunogens using the PMD (protect, modify, deprotect) technique.
  • To specifically focus the antibody response towards the cryptic face epitope of the RBD.
  • To evaluate the immunogenicity and breadth of neutralization elicited by the PMD-RBD immunogens.

Main Methods:

  • Employing the immunofocusing technique PMD to create specifically designed PMD-RBD immunogens.
  • Immunizing with PMD-RBD antigens to assess antibody responses.
  • Utilizing serum-depletion assays to confirm the skewing of the polyclonal antibody response.

Main Results:

  • PMD-RBD immunization induced robust binding antibody titers.
  • Vaccination with PMD-RBD demonstrated broad neutralizing activity against homologous and heterologous sarbecovirus strains.
  • Serum-depletion assays confirmed that PMD successfully directed the antibody response to the cryptic face of the RBD.

Conclusions:

  • The PMD technique can overcome immunodominance and refocus humoral immunity.
  • PMD-RBD immunogens are effective in eliciting broadly neutralizing antibodies against sarbecoviruses.
  • This strategy holds significant implications for developing more resilient vaccines against current and emerging viral threats.