GMMA as a ‘plug and play’ technology to tackle infectious disease to improve global health: context and perspectives for the future

ABSTRACT

Introduction

Generalized-Modules-for-Membrane-Antigens (GMMA) is a technology platform developed to design outer membrane vesicle (OMV)-based vaccines. GMMA are basically OMVs derived from a bacterial strain specifically engineered to obtain a fit-for-purpose and affordable vaccine by potentiating, or deleting, expression of specific genes. OMVs can be used as a carrier for antigens by inducing their expression on them, with the aim to improve antigen immunogenicity and design multivalent combination vaccines.

Areas Covered

We expanded this finding to show that the chemical conjugation of different proteic and/or polysaccharidic antigens, to GMMA, is a methodology complementary to the genetic manipulation to obtain highly effective combination vaccines. Here we discuss our findings with a specific focus on the impact that GMMA technology can have on global health, as this technology platform is particularly suited to support the development of affordable vaccines for low-income countries.

Expert Opinion

We believe that it is critical to elucidate the mode of action of GMMA immunogenicity and have provided a summarized description of the immunological questions to be addressed in the near future. The improved knowledge of GMMA might lead to designing more effective and safer GMMA-based vaccines to tackle the most serious vaccine-preventable diseases.

KEYWORDS:

• Carrier effect
• chemical conjugation
• global health
• GMMA
• immunogenicity
• immunological mechanisms
• low-income countries
• mode of action
• vaccines

Article highlights

• GMMA is a technology platform that can be used to design vaccines based on OMVs of Gram-negative bacteria.

• GMMA is OMVs derived from bacteria that have been through several genetic manipulations, with the aim to obtain a fit-for-purpose OMV-based vaccine. For instance, the bacterium source of GMMA can be genetically engineered to: (A) enhance the vesicle release; (B) reduce the capacity of LPS to induce reactogenicity upon OMV injection; (C) delete antigens that can be detrimental for vaccine design; (D) up-regulate antigens considered optimal candidates to have a protective efficacy of the vaccine; (E) express heterologous antigens to design combination vaccines. GMMA can be obtained for vaccine manufacturing by applying a simple method for vesicle purification.

• GMMA technology is particularly suited to the manufacturing of affordable vaccines, which makes this technology very useful to produce vaccines for low-income countries

• The first GMMA-based vaccine in clinical development is against Shigella sonnei; it demonstrated a good immunogenic potential and safety profile. Moreover, the possibility to use GMMA to design combination vaccine can make a difference, as several infections considered a serious threat in poor countries overlap the area of endemicity.

• The application of the chemical conjugation of proteic or polysaccharidic antigens to GMMA expands the potential to use this technology as a ‘plug and play’ tool to design multivalent combination vaccines.

• In the coming future, it will be particularly important to elucidate the immunological mechanisms driving GMMA to promote an optimal immune response, because they can be instrumental to optimize the design of highly effective GMMA-based vaccines. An overview of these mechanisms is presented in the Expert Opinion.

Acknowledgments

The authors thank Benn Reeve for the English revision of the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of Interests

D Piccioli, E Bartolini, and F Micoli are employees of the GSK group of companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Authorship

D Piccioli: conceived and wrote the manuscript interpreting the relevant literature, prepared the figures, and critically reviewed the manuscript.

E Bartolini: substantially contributed to the conception and design of the manuscript interpreting the relevant literature, prepared the figures and has been involved in the critical revision of the manuscript.

F Micoli: substantially contributed to the conception and design of the manuscript interpreting the relevant literature, prepared the figures and has been involved in the critical revision of the manuscript.

All authors approved the final version of the manuscript.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was sponsored by GlaxoSmithKline Biologicals SA.