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Review
. 2014;10(3):778-96.
doi: 10.4161/hv.27332. Epub 2013 Dec 3.

Recent progress in adjuvant discovery for peptide-based subunit vaccines

Fazren Azmi  1 , Abdullah Al Hadi Ahmad Fuaad, Mariusz Skwarczynski, Istvan Toth
Affiliations
Review

Recent progress in adjuvant discovery for peptide-based subunit vaccines

Fazren Azmi et al. Hum Vaccin Immunother. 2014.

Abstract

Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.

Keywords: adjuvant; dendritic cell; peptide vaccine; toll-like receptor; vaccine delivery.

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Figures

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Figure 1. The evolution of vaccines: (A) traditional vaccine utilizing a whole pathogen, (B) protein-based subunit vaccine, and (C) peptide-based subunit vaccine.
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Figure 2. Schematic overview of the immunological cascade induced by adjuvants. These immunological events are essential for enhancing and directing the adaptive immune response against vaccine antigens. The responses are primarily mediated by two main types of lymphocytes, T and B cells. (APC: Antigen Presenting Cell; CTL: Cytotoxic T Lymphocyte; NK cell: Natural killer cell; PRR: Pattern recognition receptor; TLR: Toll-like receptor; RLR: retinoic acid-inducible gene I (RIG-I)-like receptor; NLR: NOD-like receptor; MHC: Major histocompatibility complex; NLRP3: NOD-like receptor family; ASC: The inflammasome adaptor; TCR: T cell receptor; CLR: C-type lectin receptors)
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Figure 3. Chemical structure of (a) Chitosan, (b) N-trimethylated chitosan (TMC) and (c) mono-N-carboxymethyl chitosan (MCC).
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Figure 4. A schematic representation of the four-arm star polymer.
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Figure 5. The mode by which antigens are incorporated into liposomes is dependent on their chemical nature. (A) Hydrophilic antigens can be entrapped within the aqueous core of liposomes; (B) hydrophobic antigens can be conjugated at the liposome surface; (C) ampiphilic antigens can be integrated within the phospholipid bilayer.
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Figure 6. Virosomes are made up of a phospholipid bilayer which is similar to a liposome. This structure provides a platform to hold influenza virus surface protein hemagglutinin (HA) and neuraminidase (NA). Antigens are incorporated into the virosome system.
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Figure 7. Chemical structure of (A) quillaja saponin, (B) deacylated saponins, and (C) GPI-0100. The lipophilic chain (blue) was mainly responsible for the delivery of antigen, the carbohydrate residues (red) enhanced targeting to the immune cells and the aldehyde group (green) was important for co-stimulation activity.
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Figure 8. O-N intramolecular acyl migration reactions
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Figure 9. Schematic display of a repetitive antigen in a self-assembling peptide adjuvant system.
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Figure 10. (A) Chemical structure of lipid A, (B) chemical structure of MPL, and (C) and its analog: ER-803022.
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Figure 11. The correlation between supramolecular structures of lipidic chain of Lipid A (from different origins) and their effect on biological activity.
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Figure 12. A schematic presentation of muramyl dipeptide (MDP) structure that is derived from a Gram-negative bacterial cell-wall component.
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Figure 13. (A) A schematic representation of the origin MAP system, (B) an example of an LCP core based MAP system (n = total number of carbon molecules than can be varied), and (C) other immunostimulating lipid moieties.
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