Modular virus-like particles for sublingual vaccination against group A streptococcus

Area of Science:

• Vaccinology
• Immunology
• Microbial Pathogenesis

Background:

• Group A Streptococcus (GAS) infection causes significant mortality and morbidity globally, particularly in developing regions.
• Developing safe, affordable, and broadly protective GAS vaccines is challenging due to serotype diversity, antigenic variation, and risk of autoimmune responses.

Purpose of the Study:

• To evaluate a sublingual, freeze-dried (FD) formulation of modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential Group A Streptococcus vaccine.
• To assess the vaccine's ability to induce protective systemic and mucosal immunity, focusing on cost-effectiveness and applicability in endemic areas.

Main Methods:

• In vivo tracing of sublingual J8-VLPs to track lymphatic drainage and systemic absorption.
• Measurement of serum IgG and salivary IgA antibody levels following sublingual administration of J8-VLPs, with and without cholera toxin (CT) adjuvant.
• Assessment of in vitro opsonizing activity of antibodies from immunized mice against GAS.

Main Results:

• Sublingual J8-VLPs demonstrated efficient drainage to lymph nodes and rapid systemic absorption, supporting induction of both systemic and mucosal immunity.
• Vaccination induced high serum IgG and salivary IgA levels, with a balanced Th1/Th2 immune response. Co-administration with CT enhanced IgA.
• Antibodies from mice immunized with J8-VLPs (both FD and non-FD formulations) showed significant opsonizing activity against GAS in vitro.

Conclusions:

• The sublingually delivered freeze-dried formulation of modular VLPs (FD-J8-VLPs) is a safe and cost-effective strategy for inducing protective immunity against Group A Streptococcus.
• This approach effectively elicits both systemic (serum IgG) and mucosal (salivary IgA) immune responses, crucial for preventing GAS infections in endemic settings.