Review Article | Published:

Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns

Nature Reviews Immunology volume 10, pages 787796 (2010) | Download Citation

Subjects

Abstract

Researchers working on the development of vaccines face an inherent dilemma: to maximize immunogenicity without compromising safety and tolerability. Early vaccines often induced long-lived protective immune responses, but tolerability was a major problem. Newer vaccines have very few side effects but can be of limited immunogenicity. One way to tackle this problem is to design vaccines that have all the properties of pathogens with the exception of causing disease. Key features of pathogens that can be mimicked by vaccine delivery systems are their size, shape and surface molecule organization. In addition, pathogen-associated molecular patterns can be used to induce innate immune responses that promote adaptive immunity. In this Review, we discuss the approaches currently being used to optimize the delivery of antigens and enhance vaccine efficacy.

Key points

  • Vaccine-induced immune responses can be enhanced by mimicking the properties of pathogens.

  • Most vaccine delivery systems are particulate (including nanoparticles, microparticles or adjuvant-formulated proteins).

  • The size of the particle systems influences cellular targeting. The most effective sizes are in the 20–200 nm range.

  • The geometry (that is, repetitiveness) of particle surfaces is crucial for the activation of B cells, as well as for the activation of the innate humoral immune system.

  • Pathogen-associated molecular patterns (PAMPs) are crucial for the activation of dendritic cells and B cells. Some other receptors of the innate immune system may also be involved in this process.

  • For effective vaccines, PAMPs should be physically linked to the antigens to enhance their activity and reduce side effects.

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Acknowledgements

We thank V. Manolova, J. Bessa, T. Kündig, A. Link and P. Saudan for critically reading the manuscript and for their helpful comments.

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  1. Research, Cytos Biotechnology AG, Wagistrasse 25, 8952 Schlieren-Zürich, Switzerland.

    • Martin F. Bachmann
    •  & Gary T. Jennings

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Competing interests

Martin F. Bachmann and Gary T. Jennings are employees of Cytos Biotechnology AG, Zurich, Switzerland, and hold stocks or stock options in the company.

Corresponding author

Correspondence to Martin F. Bachmann.

Glossary

Particulate adjuvant

An adjuvant that forms small particles or droplets and entraps the antigen.

Cross-presentation

The ability of certain antigen-presenting cells to load peptides that are derived from exogenous antigens onto MHC class I molecules. This property is atypical, because most cells exclusively present peptides from their endogenous proteins on MHC class I molecules. Cross-presentation is essential for the initiation of immune responses to viruses that do not infect antigen-presenting cells.

Immune complex

A complex of antigen bound to antibody and, sometimes, components of the complement system. The levels of immune complexes are increased in many autoimmune disorders, in which they become deposited in tissues and cause tissue damage. To effectively activate complement and Fc receptors, more than one antibody needs to be present in a complex.

Subcapsular sinus macrophage

A specialized macrophage that resides in the subcapsular sinus of lymph nodes and is efficient at capturing antigen from the lymph.

Follicular DC

(FDC). A cell that has a dendritic morphology and is present in lymph nodes. These cells display on their surface intact antigens that are held in immune complexes, and B cells present in the lymph node can interact with these antigens. FDCs are of non-haematopoietic origin and are not related to dendritic cells.

Langerhans cell

A professional antigen-presenting dendritic cell localized in the epidermis of the skin.

Depot

An antigen depot refers to antigen persisting at the site of injection, causing prolonged exposure of the immune system to the antigen. Many adjuvants induce antigen depot formation.

Plasmacytoid DC

A cell that has a plasma cell-like morphology and produces high levels of type I interferons after exposure to viruses.

CpG

A DNA motif rich in non-methylated CG motifs that is mainly found in bacterial or viral DNA and is recognized by Toll-like receptor 9.

Hapten

A molecule that can bind antibody but cannot elicit an immune response by itself. Antibodies that are specific for a hapten can be generated when the hapten is chemically linked to a protein carrier that can elicit a T cell response.

CD19–CD21

Co-stimulatory molecules for B cells. CD21 binds complement degradation products, and CD19 is the signal transduction molecule for CD21.

Germinal centre

Transient, highly organized multicellular structure present within B cell follicles that is essential for the generation of memory B cells and long-lived plasma cells, as well as for affinity maturation of antibodies.

T follicular helper cell

A specialized T helper cell found in B cell follicles. These cells require interleukin-21 for their development and are specialized in providing help to B cells.

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