Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines

Moyle, Peter Michael (2017) Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines. Biotechnology Advances, 35 3: 375-389. doi:10.1016/j.biotechadv.2017.03.005


Author Moyle, Peter Michael
Title Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines
Journal name Biotechnology Advances   Check publisher's open access policy
ISSN 0734-9750
1873-1899
Publication date 2017-03-08
Year available 2017
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.biotechadv.2017.03.005
Open Access Status Not yet assessed
Volume 35
Issue 3
Start page 375
End page 389
Total pages 15
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Subject 1305 Biotechnology
Abstract Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their mechanisms of action, structural or sequence requirements for activity, sequence modifications to enhance their activity or simplify production, adverse effects, and examples of vaccines in preclinical or human clinical trials.
Keyword Adjuvants
Extra domain A
Flagellin
Fusion Proteins
Heat Shock Protein
Lipopeptide
subunit vaccines
Toll-like Receptors
Vaccines
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 2014002917
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
School of Pharmacy Publications
 
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Created: Wed, 15 Mar 2017, 08:44:47 EST by Peter Moyle on behalf of School of Pharmacy