Abstract
BACKGROUND AND OBJECTIVES: Generalized modules for membrane antigens (GMMA) are outer membrane vesicles derived from gram-negative bacteria that can be used to design affordable subunit vaccines. GMMA are highly immunogenic and capable to induce an optimal antigen-specific humoral immune response both in animals and humans. Despite their potent immunogenicity, GMMA are usually formulated with aluminum salts (alum) to reduce their potential systemic reactogenicity. GMMA, in fact, contain agonists of toll-like receptor 4 (TLR4) and TLR2 that possess pro-inflammatory activity. The adsorption of GMMA onto alum is believed to reduce their systemic exposure. However, it has been found that GMMA formulated without alum did not induce concerning signs of systemic reactogenicity in the rabbit model. Here, we asked whether GMMA promote local reactogenicity. METHODS: We immunized mice intramuscularly with GMMA alone or adsorbed to alum and analyzed the injection site during 7 days after treatment. RESULTS: We found that GMMA alone promoted only mild inflammation within the muscle, whereas the presence of alum induced severe muscle inflammation, as expected. Thus, in the mouse model, GMMA demonstrated to possess mild local reactogenic potential, while alum is confirmed a major driver of local reactogenicity. CONCLUSION: Our results further support the idea to investigate the reactogenicity of GMMA formulated without alum in clinical studies.