Self-adjuvanting vaccine against group A streptococcus: Application of fibrillized peptide and immunostimulatory lipid as adjuvant

Fazren Azmi, Abdullah Al Hadi Ahmad Fuaad, Ashwini Kumar Giddam, Michael R. Batzloff, Michael F. Good, Mariusz Skwarczynski, Istvan Toth

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity. Recently, fibril-forming peptides such as Q11 and lipoamino acid-based carrier have been identified to induce substantial immune responses when covalently linked to peptide epitope. In this study, we have incorporated either Q11 or lipoamino acids to a peptide epitope (J14) derived from M protein of group A streptococcus to develop self-adjuvanting vaccines. J14, Q11 and lipoamino acids were also conjugated together in a single vaccine construct in an attempt to evaluate the synergy effect of combining multiple adjuvants. Physicochemical characterization demonstrated that the vaccine constructs folded differently and self-assembled into nanoparticles. Significantly, only vaccine constructs containing double copies of lipoamino acids (regardless in conjugation with Q11 or not) were capable to induce significant dendritic cells uptake and subsequent J14-specific antibody responses in non-sizes dependent manners. Q11 had minimal impact in enhancing the immunogenicity of J14 even when it was used in combination with lipoamino acids. These findings highlight the impact of lipoamino acids moiety as a promising immunostimulant carrier and its number of attachment to peptide epitope was found to have a profound effect on the vaccine immunogenicity.

Original languageEnglish
Pages (from-to)6401-6408
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number22
DOIs
Publication statusPublished - 15 Nov 2014

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Streptococcus
Vaccines
Lipids
Peptides
Acids
Epitopes
Antigens
Immunologic Adjuvants
Nanoparticles
Dendritic Cells
Antibody Formation
Safety
Antibodies
Proteins

Keywords

  • Delivery
  • Fibril
  • Group A streptococcus
  • Lipopeptide
  • Peptide
  • Vaccine

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Self-adjuvanting vaccine against group A streptococcus : Application of fibrillized peptide and immunostimulatory lipid as adjuvant. / Azmi, Fazren; Ahmad Fuaad, Abdullah Al Hadi; Giddam, Ashwini Kumar; Batzloff, Michael R.; Good, Michael F.; Skwarczynski, Mariusz; Toth, Istvan.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 22, 15.11.2014, p. 6401-6408.

Research output: Contribution to journalArticle

Azmi, Fazren ; Ahmad Fuaad, Abdullah Al Hadi ; Giddam, Ashwini Kumar ; Batzloff, Michael R. ; Good, Michael F. ; Skwarczynski, Mariusz ; Toth, Istvan. / Self-adjuvanting vaccine against group A streptococcus : Application of fibrillized peptide and immunostimulatory lipid as adjuvant. In: Bioorganic and Medicinal Chemistry. 2014 ; Vol. 22, No. 22. pp. 6401-6408.
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