title: Comparison of the immune responses to the CIA06-adjuvanted human papillomavirus L1 VLP vaccine with those against the licensed HPV vaccine Cervarix™ in mice.
abstract: CIA05 is a toll-like receptor (TLR) 4 agonist derived from an Escherichia coli lipopolysaccharide (LPS) mutant and has been shown to have potential as a vaccine adjuvant. In this study, we investigated the immunopotentiating activity of the adjuvant system CIA06, which is comprised of CIA05 and aluminum hydroxide (alum), when used with the human papillomavirus (HPV) L1 virus-like particles (VLPs) vaccine. BALB/c mice were immunized intramuscularly three times at 2-week intervals with HPV16 L1 VLPs alone or in the presence of various combinations of CIA05 and alum, and the immune responses were assessed. We found that the combination of CIA05 and alum at a ratio of 1:50 (designated CIA06B) yielded the highest immune response in terms of serum anti-HPV L1 VLP IgG antibody titers, splenocyte interferon (IFN)-γ secretion, and antigen-specific memory B cell responses. The immunogenicity of the CIA06B-adjuvanted HPV16/18 L1 VLP vaccine was compared with that of the currently licensed HPV vaccine Cervarix™. The CIA06B-adjuvanted vaccine was similar to Cervarix™ with regard to eliciting serum antigen-specific IgG antibodies and virus-neutralizing antibodies but more effective at inducing splenic cytokine production and memory B cells. We also observed that the antigen-specific IgG antibody titers, splenic IFN-γ secretion and memory B cells induced by the CIA06B-adjuvanted HPV vaccine remained high up to 24 weeks post-immunization. Based on these data, we concluded that CIA06B may have potential as an adjuvant in a potent prophylactic vaccine against HPV infection.
authors.affiliation: Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Han
authors.forename: Seo Ri
authors.initials: SR
authors.lastname: Wui
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Park
authors.forename: Na Gyong
authors.initials: NG
authors.lastname: Lee
authors.forename: Kwang Sung
authors.initials: KS
authors.lastname: Kim
authors.forename: Yang Je
authors.initials: YJ
authors.lastname: Cho
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hong-Jin
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000302:isolation & purification; D000534:Alum Compounds / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000737:chemistry; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D022721:Vaccines, Virosome; C041524:aluminum sulfate; D007371:Interferon-gamma