title: Carrageenan as an adjuvant to enhance peptide-based vaccine potency.
abstract: New innovative therapies are urgently required in order to combat the high mortality and morbidity associated with advanced cancers. Antigen-specific cancer immunotherapy using peptide-based vaccination has emerged as an attractive approach for the control of cancers due to its simplicity and easy preparation. However, such an approach requires the employment of suitable adjuvants. In the current study, we explored the employment of a sulfated polysaccharide compound from red algae, carrageenan (CGN) as an adjuvant for their ability to generate antigen-specific immune responses and antitumor effects in mice vaccinated with human papillomavirus type 16 (HPV-16) E7 peptide vaccine. We found that carrageenan can significantly enhance the E7-specific immune responses generated by E7 peptide vaccination via the TLR4 activation pathway. In addition, carrageenan could enhance the protective and therapeutic antitumor effects generated by E7 peptide vaccination against E7-expressing tumors. Furthermore, the observed enhancement was not restricted to E7 antigen but was also applicable to other antigenic systems. We also found that other structurally similar compounds to CGN, such as dextran, also generated similar immune enhancement. Thus, our data suggest that CGN and its structurally related compounds may serve as innovative adjuvants for enhancing peptide-based vaccine potency.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Ya-Chea
authors.initials: YC
authors.lastname: Tsai
authors.forename: Archana
authors.initials: A
authors.lastname: Monie
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002351:Carrageenan / Q000276:immunology* / Q000494:pharmacology; D003911:Dextrans / Q000276:immunology / Q000494:pharmacology; D005260:Female; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000517:prevention & control / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D003911:Dextrans; D008050:Lipid A; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D022223:Vaccines, Subunit; C059731:oncogene protein E7, Human papillomavirus type 16; D002351:Carrageenan; C048436:monophosphoryl lipid A