Multiple antigen presenting system (MAPS): state of the art and potential applications

ABSTRACT

Introduction

Technological innovations have been instrumental in advancing vaccine design and protective benefit. Improvements in the safety, tolerability, and efficacy/effectiveness profiles have profoundly reduced vaccine-preventable global disease morbidity and mortality. Here we present an original vaccine platform, the Multiple Antigen Presenting System (MAPS), that relies on high-affinity interactions between a biotinylated polysaccharide (PS) and rhizavidin-fused pathogen-specific proteins. MAPS allows for flexible combinations of various PS and protein components.

Areas covered

This narrative review summarizes the underlying principles of MAPS and describes its applications for vaccine design against bacterial and viral pathogens in non-clinical and clinical settings.

Expert opinion

The utilization of high-affinity non-covalent biotin–rhizavidin interactions in MAPS allows for combining multiple PS and disease-specific protein antigens in a single vaccine. The modular design enables a simplified exchange of vaccine components. Published studies indicate that MAPS technology may support enhanced immunogenic breadth (covering more serotypes, inducing B- and T-cell responses) beyond that which may be elicited via PS- or protein-based conjugate vaccines. Importantly, a more detailed characterization of MAPS-based candidate vaccines is warranted, especially in clinical studies. It is anticipated that MAPS-based vaccines could be adapted and leveraged across numerous diseases of global public health importance.

Plain Language Summary

Existing conjugate vaccines, consisting of pathogen-derived polysaccharides (PSs) and carrier proteins unrelated to the target pathogen, have helped to significantly reduce morbidity and mortality of several bacterial diseases. However, the worldwide burden of infectious diseases targeted by conjugate vaccines is still high. This is mainly due to high pathogen diversity and ongoing evolution, and innovative approaches are needed to respond to these challenges. Multiple Antigen Presenting System (MAPS) is an original vaccine technology that relies on strong molecular interactions between biotin and rhizavidin. MAPS is highly adaptable, as different PS and protein components can be precisely combined and easily exchanged, with limited damage to immunogenic epitopes (PS and protein features recognized by the immune system). Unlike existing conjugate vaccines, MAPS complexes contain pathogen-specific proteins, able to elicit broad immune responses directed against the pathogen. To date, investigational MAPS-based vaccines have been evaluated in several non-clinical studies; one candidate pneumococcal vaccine has been evaluated in early phase clinical studies in healthy children and adults (including older adults). In these clinical studies, the MAPS-based vaccine candidate was well tolerated and induced robust immune responses. If the favorable profile of MAPS-based vaccines is confirmed in further studies, these vaccines could be used against infectious diseases associated with significant morbidity and mortality.

GRAPHICAL ABSTRACT

KEYWORDS:

• Bacterial vaccines
• biotin–rhizavidin interaction
• cell-mediated immunity
• glycocomplex
• MAPS
• multiple antigen presenting system
• pneumococcal vaccines
• polysaccharide-specific antibodies

Article highlights

• Several aspects of infectious diseases, such as diverse mechanisms of pathogenesis, high diversity and evolution of etiological agents, serotype replacement, and emergence of new pathogens, call for development of novel and more effective vaccines.

• Multiple Antigen Presenting System (MAPS) is a unique vaccine platform that uses high-affinity biotin–rhizavidin interaction to combine polysaccharides and target-pathogen-specific proteins into macromolecular complexes.

• MAPS complexes are stable, precisely defined (controlled ratio of components), modular (components easily exchanged and combined), flexible (combination of components of different origin/property), and epitope-preserving (single-point attachment between polysaccharide and protein).

• In non-clinical studies, MAPS-based candidate vaccines against six bacterial and one viral target were able to induce broader (antibody- and cell-mediated) immune responses compared to licensed vaccines targeting the same pathogens or purified protein controls.

• In clinical studies, a 24-valent MAPS-based pneumococcal candidate vaccine (AFX3772) was shown to be well tolerated and induced robust immune responses in healthy adults (including older adults).

• Inclusion of conserved pathogen-specific proteins in MAPS complexes may potentiate the protection mediated by polysaccharide-specific immunity via eliciting serotype-independent and multifaceted humoral and cellular responses (e.g. helper T cells [Th]1 and Th17 and cytotoxic T cells).

• MAPS technology may provide a platform to support advanced vaccine development across various disease targets and overcome some inherent limitations of current technologies.

Abbreviations

AE, adverse event; CD4⁺ and CD8⁺, cluster-of-differentiation-4- and −8-expressing; CPS, capsular polysaccharide; γδT, gamma delta T cells; GI, gastrointestinal; GMC, geometric mean concentration; GMMA, Generalized Modules for Membrane Antigens; IFN-γ, interferon-gamma; IgG, immunoglobulin G; IL-17A, interleukin-17A; MAPS, Multiple Antigen Presenting System; Mtb, Mycobacterium tuberculosis; NKT, natural killer T cells; OPA, opsonophagocytic activity; PCV, pneumococcal conjugate vaccine; PPSV23, pneumococcal polysaccharide vaccine; PS, polysaccharide; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; Th1, Th2, and Th17, T helper cells 1, 2, and 17; TNF-α, tumor necrosis factor-alpha.

Declaration of interests

R Malley is a former employee of GSK and was an Affinivax board member and scientific founder at the time this manuscript was initiated. R Malley receives consulting fees from GSK as a consultant in the field of vaccines and discloses GSK support for attending meetings and/or travel and participation to the GSK Advisory board. F Zhang and YJ Lu received consulting fees from Affinivax and GSK as consultants. R Malley, F Zhang, and YJ Lu declare potential future payments and royalties as equity holders of Affinivax and named co-inventors of MAPS technology. R Malley, F Zhang, and YJ Lu have issued or pending patents on MAPS technology. S Sebastian has issued and pending patents on Multivalent Pneumococcal Vaccine. DO Willer has restricted share stock ownership in GSK. S Sebastian and DO Willer are employees of the GSK group of companies. None of the authors have any other financial or non-financial interests to declare. 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 material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

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

Author contributions

All authors contributed substantially to the conception and design of the review article and interpreting the relevant literature and were involved in writing the review article and revised it for intellectual content. All authors contributed equally to manuscript development and have approved the final version of the manuscript.

Acknowledgments

The authors thank Akkodis Belgium for providing manuscript writing (Irena Zurnic Bönisch) and coordination support on behalf of GSK.

Additional information

Funding

This manuscript was funded by GlaxoSmithKline Biologicals SA.