Supramolecular peptide vaccines: tuning adaptive immunity

doi:10.1016/j.coi.2015.06.007

Current Opinion in Immunology

Volume 35, August 2015, Pages 73-79

https://doi.org/10.1016/j.coi.2015.06.007 Get rights and content

Highlights

•
Successful immunotherapies must target a precise phenotype and strength of an immune response.
•
Supramolecular materials may offer strategies for identifying and eliciting such phenotypes.
•
Comparative studies of how material properties influence immune phenotypes are in early stages.

Successful immunotherapies must be designed to elicit targeted immune responses having a specifiable phenotype across many dimensions, including the phenotypes of T cells, B cells, antigen-presenting cells, and others. For synthetic or subunit vaccines, stimulation of strong enough immune responses usually requires adjuvants, which can cause local inflammation and complicate the targeting of such phenotypes. Supramolecular materials provide routes for reducing or eliminating supplemental adjuvants. Owing to their compositional controllability, supramolecular assemblies show promise for fine-tuning immune responses by adjusting combinations of material attributes including epitope content, multivalency, size, dose, and small quantities of specific adjuvants. Here we focus on supramolecular vaccines incorporating multiple epitopes in precise ratios, with an emphasis on peptides that form high-aspect ratio (i.e. fibrillar) structures.

Graphical abstract

Section snippets

Introduction: the need for tuned immunotherapies

A successfully engineered immunotherapy elicits a specific immune phenotype by orchestrating the activities of a broad range of different immune cells [1, 2, 3, 4]. However, in some cases this ideal phenotype is not easily achieved or even ascertained, and there remain many infectious and non-infectious conditions that have yet to be treatable using vaccines and other immunotherapies. In this short review, we will discuss supramolecular assemblies, primarily those composed of peptides and

Examples of supramolecular peptide vaccines

Supramolecular peptide assemblies usually take the form of nanofibers, nanoparticles, or gels, and are stabilized by non-covalent forces (hydrophobic interactions, hydrogen bonding, and electrostatic interactions). Their immunological properties arise from their size and shape, their particulate nature, their multivalency, and their ability to mix multiple different functional components with stoichiometric precision [1, 18••, 19••, 20] (Figure 1). By attaching different epitopes to a

Current challenges and future development

While some supramolecular vaccines can stimulate particular immune responses without additional adjuvants, several aspects of their mechanism of adjuvancy remain unclear. First, because many different supramolecular platforms have been developed largely independently by different research groups, a systematic comparison of each platform's mechanism of action has yet to be conducted. Different platforms may engage different mechanisms, including TLR activation, inflammasome signaling, autophagy,

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

We thank Rebecca Pompano for helpful comments on the manuscript. Work in our group on supramolecular immunologically active materials has been funded by the National Institutes of Health, Grant numbers AI094444 and AI118182 (NIAID), EB009701 (NIBIB), and AR066244 (NIAMS).

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View full text

Supramolecular peptide vaccines: tuning adaptive immunity

Highlights

Graphical abstract

Section snippets

Introduction: the need for tuned immunotherapies

Examples of supramolecular peptide vaccines

Current challenges and future development

References and recommended reading

Acknowledgements

Engineering synthetic vaccines using cues from natural immunity

Nat Mater

Engaging adaptive immunity with biomaterials

J Mater Chem B

Engineering approaches to immunotherapy

Sci Transl Med

Engineering vaccines and niches for immune modulation

Acta Biomater

Differentiation of effector CD4 T cell populations

Annu Rev Immunol

Follicular helper CD4 T cells (TFH)

Annu Rev Immunol

A temporal model of human IgE and IgG antibody function

Front Immunol

From vaccines to memory and back

Immunity

B lymphocytes: how they develop and function

Blood

Vaccine adjuvants: putting innate immunity to work

Immunity

More than one reason to rethink the use of peptides in vaccine design

Nat Rev Drug Discov

Vaccine stabilization: research, commercialization, and potential impact

Vaccine

Vaccine adjuvants: current state and future trends

Immunol Cell Biol

Key roles of adjuvants in modern vaccines

Nat Med

Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists

Expert Rev Vaccines

Biomaterials for nanoparticle vaccine delivery systems

Pharm Res

Micro and nanoparticle-based delivery systems for vaccine immunotherapy: an immunological and materials perspective

Adv Healthc Mater

Gradated assembly of multiple proteins into supramolecular nanomaterials

Nat Mater

Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs

Adv Healthc Mater

Co-assembling peptides as defined matrices for endothelial cells

Biomaterials

Ovalbumin lipid core peptide vaccines and their CD4+ and CD8+ T cell responses

Vaccine

Engineered synthetic virus-like particles and their use in vaccine delivery

Chembiochem

Self-assembled peptide amphiphile micelles containing a cytotoxic T-cell epitope promote a protective immune response in vivo

Adv Mater

Protective antibody and CD8+ T-cell responses to the Plasmodium falciparum circumsporozoite protein induced by a nanoparticle vaccine

PLoS One

Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide vaccine in HLA transgenic mice

Vaccine

The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation

Biomaterials

Generation of effector memory T cell-based mucosal and systemic immunity with pulmonary nanoparticle vaccination

Sci Transl Med

Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction

Proc Natl Acad Sci U S A