Abstract
Generalized Modules for Membrane Antigens (GMMA) are outer membrane vesicles derived from Gram-negative bacteria engineered to provide an over-vesiculating phenotype, which represent an attractive platform for the design of affordable vaccines. GMMA can be further genetically manipulated to modulate the risk of systemic reactogenicity and to act as delivery system for heterologous polysaccharide or protein antigens. GMMA are able to induce strong immunogenicity and protection in animal challenge models, and to be well-tolerated and immunogenic in clinical studies. The high immunogenicity could be ascribed to their particulate size, to their ability to present to the immune system multiple antigens in a natural conformation which mimics the bacterial environment, as well as to their intrinsic self-adjuvanticity. However, GMMA mechanism of action and the role in adjuvanticity are still unclear and need further investigation. In this review, we discuss progresses in the development of the GMMA vaccine platform, highlighting successful applications and identifying knowledge gaps and potential challenges.
Highlights
Both pathogenic and nonpathogenic Gram-negative bacteria are able to spontaneously release 25– 250 nm vesicles during growth, especially during the end of log phase [1]
Generalized Modules for Membrane Antigens (GMMA) constitute a straightforward technology based on lowcost of production and high purification yields and is suitable for the development of vaccines against bacterial pathogens and of affordable vaccines targeting lowand middle-income countries (LMICs)
Based on recent results not yet published from a controlled human infection model (CHIM) study, it seems that Shigella LPS amount is critical to induce a level of IgG antibodies able to protect from Shigella infection and additional work has been done for improving the design of a 4-component Shigella GMMA-based vaccine that is entering clinical testing
Summary
Both pathogenic and nonpathogenic Gram-negative bacteria are able to spontaneously release 25– 250 nm vesicles during growth, especially during the end of log phase [1] Since they originate from the bacterial outer membrane, these vesicles reflect the membrane composition and are named outer membrane vesicles (OMVs). They contain bacterial antigens such as lipopolysaccharides (LPS) and proteins in their original environment, and additional immunostimulatory molecules (i.e. lipoproteins, peptidoglycans). Because of their composition, they raise high scientist interest and have been widely investigated as a promising vaccine platform [2, 3]. We will discuss progress in the development of the GMMA vaccine platform, highlighting successful applications, gaps and potential challenges
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