Chiral-Structured Aluminum Oxyhydroxide Nanoadjuvants for Prophylactic Vaccines

Area of Science:

• Materials Science
• Immunology
• Nanotechnology

Background:

• Biomaterial chirality influences biological interactions, impacting cellular uptake, receptor binding, and immune activation.
• Aluminum-based adjuvants are widely used in vaccines, but the role of chirality in their immunological performance is not well understood.
• Optimizing physicochemical properties of adjuvants is crucial for enhancing vaccine efficacy.

Purpose of the Study:

• To investigate the impact of chirality on aluminum oxyhydroxide (AlOOH) nanoadjuvants' immunological performance.
• To develop a chiral engineering strategy for AlOOH nanoadjuvants using enantiomeric lysine hydrochloride.
• To explore the mechanism of chirality-controlled antigen delivery and its effect on humoral immunity.

Main Methods:

• Chiral engineering of aluminum oxyhydroxide (AlOOH) nanoadjuvants using l- or d-lysine hydrochloride as structure-directing agents.
• Characterization of nanoadjuvant crystal growth and modulation of anisotropic atomic arrangements.
• Adsorption studies using human papillomavirus (HPV) type 18 L1 virus-like particles (VLPs) and in vitro/in vivo vaccination models (HPV, hepatitis B surface antigen).
• Assessment of antigen release, lymph node trafficking, dendritic cell uptake, and antigen-specific antibody titers.

Main Results:

• l-lysine inhibited longitudinal growth of l-AlOOH, inducing chiral structures with a lower aspect ratio.
• l-AlOOH showed a lower adsorption coefficient for chiral HPV 18 L1 VLPs due to chirality mismatch, leading to accelerated antigen release and lymph node trafficking.
• l-AlOOH significantly enhanced antigen uptake by dendritic cells and boosted antigen-specific antibody titers in vaccination models compared to achiral and d-AlOOH.
• Chirality-controlled antigen delivery by l-AlOOH modulated humoral immunity.

Conclusions:

• The chiral configuration of AlOOH nanoadjuvants critically modulates their adjuvanticity.
• Chirality-driven antigen delivery is a key mechanism for enhancing vaccine immune responses.
• This study provides a blueprint for designing next-generation vaccine adjuvants with tailored chiral properties.