Chemically Modified Bacterial Sacculi as a Vaccine Microparticle Scaffold.

Area of Science:

• Immunology
• Materials Science
• Biotechnology

Background:

• Subunit vaccines often require scaffolds or carrier proteins to enhance immunogenicity.
• Bacterial peptidoglycan (PGN) is a biocompatible and abundant component of bacterial cell walls.

Purpose of the Study:

• To develop and characterize a novel microparticle vaccine scaffold using bacterial peptidoglycan (PGN).
• To evaluate the efficacy of PGN microparticles for conjugating immunogens and eliciting immune responses.

Main Methods:

• Isolation of intact bacterial peptidoglycan (PGN) sacculi to form microparticles.
• Modification of PGN microparticles with bio-orthogonal chemical handles for site-specific immunogen conjugation.
• Evaluation of PGN microparticle immunogenicity and conjugation efficiency using Staphylococcus aureus derived PGN.
• Conjugation of SARS-CoV-2 receptor-binding domain (RBD) to PGN microparticles and assessment of elicited antibody titers.

Main Results:

• PGN microparticles were successfully purified, characterized, and shown to be immunogenic.
• Optimization of PGN modification using Staphylococcus aureus PGN with azido-d-alanine enabled robust immunogen conjugation.
• PGN microparticle scaffolds elicited immunostimulation comparable to the conventional carrier protein keyhole limpet hemocyanin (KLH).
• A conjugate vaccine using S. aureus PGN microparticles with SARS-CoV-2 RBD induced comparable neutralizing antibody titers to KLH-conjugated RBD.

Conclusions:

• Chemically modified bacterial PGN microparticles represent a versatile, biodegradable scaffold for vaccine development.
• This novel scaffold facilitates site-specific immunogen attachment and elicits robust immune responses.
• PGN microparticle-based conjugate vaccines show promise for eliciting protective immunity against target antigens.