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

Black, Matthew, Trent, Amanda, Tirrell, Matthew and Olive, Colleen (2010) Advances in the design and delivery of peptide subunit vaccines with a focus on Toll-like receptor agonists. Expert Review of Vaccines, 9 2: 157-173. doi:10.1586/ERV.09.160


Author Black, Matthew
Trent, Amanda
Tirrell, Matthew
Olive, Colleen
Title Advances in the design and delivery of peptide subunit vaccines with a focus on Toll-like receptor agonists
Journal name Expert Review of Vaccines   Check publisher's open access policy
ISSN 1476-0584
1744-8395
Publication date 2010-02-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1586/ERV.09.160
Open Access Status Not Open Access
Volume 9
Issue 2
Start page 157
End page 173
Total pages 17
Editor Adam Williams
Place of publication London, United Kingdom
Publisher Expert Reviews
Language eng
Abstract Traditional vaccines derived from attenuated or inactivated pathogens are effective at inducing antibody-based protective immune responses but tend to be highly reactogenic, causing notable adverse effects. Vaccines with superior safety profiles can be produced by subunit approaches, utilizing molecularly defined antigens (e.g., proteins and polysaccharides). These antigens, however, often elicit poor immunological responses, necessitating the use of adjuvants. Immunostimulatory adjuvants have the capacity to activate antigen presenting cells directly through specific receptors (e.g., Toll-like receptors (TLRs)), resulting in enhanced presentation of antigens as well as the secretion of proinflammatory chemokines and cytokines. Consequently, innate immune responses are amplified and adaptive immunity is generated. Recently, site-specific conjugation of such immunostimulatory adjuvants (e.g., TLR ligands) onto defined antigens has shown superior efficacy over unconjugated mixtures, suggesting that the development of chemically characterized immunostimulatory adjuvants and optimized approaches for their conjugation with antigens may provide a better opportunity for the development of potent, novel vaccines. This review briefly summarizes various TLR agonists utilized as immunostimulatory adjuvants and focuses on the development of techniques (e.g., recombinant, synthetic, and semisynthetic) for generating adjuvant-antigen fusion vaccines incorporating peptide or protein antigens.
Formatted abstract
Considerable success has been made with many peptide antigen formulations, and peptide-based vaccines are emerging as the next generation of prophylactic and remedial immunotherapy. However, finding an optimal platform balancing all of the requirements for an effective, specific and safe immune response remains a major challenge for many infectious and chronic diseases. This review outlines how peptide immunogenicity is influenced by the way in which peptides are presented to the immune system, underscoring the need for multifunctional delivery systems that couple antigen and adjuvant into a single construct. Particular attention is given to the ability of Toll-like receptor agonists to act as adjuvants. A survey of recent approaches to developing peptide antigen delivery systems is given, many of which incorporate Toll-like receptor agonists into the design.
Keyword Antigen delivery system
Liposome
Micelle
Nanoparticle
Peptide
Subunit vaccine
Toll-like receptor
Virus-like particle
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Non HERDC
School of Public Health Publications
School of Medicine Publications
 
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Created: Mon, 04 Apr 2011, 22:27:55 EST by Debbie Banks on behalf of !NON-HERDC