Safe Staphylococcal Platform for the Development of Multivalent Nanoscale Vesicles against Viral Infections

Area of Science:

• Microbiology
• Immunology
• Vaccine Development

Background:

• Viruses often possess multiple serotypes, necessitating multivalent vaccines for comprehensive protection.
• Bacterial membrane vesicles (MVs) are explored as platforms for delivering diverse antigens.

Purpose of the Study:

• To engineer Staphylococcus aureus-derived nanoscale vesicles (^ΔagrMVs) for the presentation of heterologous viral antigens.
• To evaluate the immunogenicity and protective efficacy of engineered ^ΔagrMVs against dengue virus (DENV).

Main Methods:

• Constructed an agr locus deletion mutant of Staphylococcus aureus (RN4220-Δagr) to produce nanoscale vesicles (^ΔagrMVs).
• Fused bacterial protein components with FLAG tags and incorporated DENV envelope E domain III proteins (EDIIIconA, EDIIIconB) into ^ΔagrMVs.
• Administered engineered ^ΔagrMVs to mice and assessed antibody production and protective immunity against DENV challenge.

Main Results:

• Engineered ^ΔagrMVs successfully presented tagged bacterial proteins and DENV EDIII antigens.
• Immunization with engineered ^ΔagrMVs elicited antibodies recognizing all four DENV serotypes.
• Sera from immunized mice provided protection against DENV-2 challenge in cell culture and animal models.

Conclusions:

• Engineered bacterial membrane vesicles serve as a promising platform for developing multivalent viral vaccines.
• This approach offers a novel strategy for creating effective vaccines against viruses with multiple serotypes, such as dengue virus.