Synthesis, Characterization and Immunological Evaluation of Self‐Adjuvanting Group A Streptococcal Vaccine Candidates Bearing Various Lipidic Adjuvanting Moieties

Fagan, Vincent; Hussein, Waleed M.; Su, Mei; Giddam, Ashwini Kumar; Batzloff, Michael R.; Good, Michael F.; Tóth, István; Simerská, Pavla

doi:10.1002/cbic.201600639

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…Although exciting, hydrophobic association is not the only method available for achieving adjuvant incorporation. Covalent coupling antigens to Pam 2 C have been previously shown to enhance peptide immunogenicity (40,47) and the chemical similarities between Pam 2 K and Pam 2 C potentially allow for direct adjuvant micelle templating. The results support this idea as Pam 2 C-OVA BT -(KE) 4 readily selfassembled in water at a low CMC (0.32 μM-Fig.…”

Section: Discussionmentioning

confidence: 99%

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity

Zhang

Kramer

Smith

et al. 2018

AAPS J

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Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin-OVA) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-PamC), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

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Section: Discussionmentioning

confidence: 99%

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity

Zhang

Kramer

Smith

et al. 2018

AAPS J

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“…A simplified analogue of Pam 2 Cys was designed by replacing the Cys and glycerol moieties in Pam 2 Cys with Ser residue [139,149]. Dipalmitoyl serine (DPS) demonstrated an adjuvanting ability similar to Pam 2 Cys and an affinity to TLR2.…”

Section: Development Of Adjuvants and Delivery Systems For Gas Pepmentioning

confidence: 99%

“…Dipalmitoyl serine (DPS) demonstrated an adjuvanting ability similar to Pam 2 Cys and an affinity to TLR2. Similarly, an analogue of Pam 3 Cys was designed by the chemical binding of three dodecanoylated lysine moieties, which upon conjugation with J8 was able to induce the same level of antibody titres as DPS [149].…”

Section: Development Of Adjuvants and Delivery Systems For Gas Pepmentioning

confidence: 99%

Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

et al. 2019

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Group A Streptococcus (GAS) infection can cause a variety of diseases in humans, ranging from common sore throats and skin infections, to more invasive diseases and life-threatening post-infectious diseases, such as rheumatic fever and rheumatic heart disease. Although research has been ongoing since 1923, vaccines against GAS are still not available to the public. Traditional approaches taken to develop vaccines for GAS failed due to poor efficacy and safety. Fortunately, headway has been made and modern subunit vaccines that administer minimal bacterial components provide an opportunity to finally overcome previous hurdles in GAS vaccine development. This review details the major antigens and strategies used for GAS vaccine development. The combination of antigen selection, peptide epitope modification and delivery systems have resulted in the discovery of promising peptide vaccines against GAS; these are currently in preclinical and clinical studies.

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“…15). 101,102 All glycolipid conjugates self-assembled into helical structures with 76-79 eliciting similar antibody titers whilst 76, being the least helical, gave titers 100-fold less. 102 In summary, various glycolipids have been used as immunoadjuvants, conjugated with different antigens.…”

Section: Reviewmentioning

confidence: 99%

Recent progress in synthetic self-adjuvanting vaccine development

et al. 2022

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Synthesis, Characterization and Immunological Evaluation of Self‐Adjuvanting Group A Streptococcal Vaccine Candidates Bearing Various Lipidic Adjuvanting Moieties

Cited by 11 publications

References 40 publications

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity

Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

Recent progress in synthetic self-adjuvanting vaccine development

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