A nontoxic derivative of lipopolysaccharide increases immune responses to Gardasil HPV vaccine in mice.
Human papillomavirus (HPV) is the causative agent of cervical cancer, the second most common cause of cancer death in women worldwide. The licensed HPV vaccine Gardasil((R)) from Merck & Co. is a quadrivalent vaccine containing virus-like particles (VLPs) of the L1 proteins from HPV types 6, 11, 16, and 18 adsorbed on aluminum salts (alum). CIA07 is an immunostimulatory agent comprised of bacterial DNA fragments (CIA02) and a nontoxic derivative of lipopolysaccharide (CIA05) that has been shown to have antitumor activity and adjuvant activity for viral and bacterial vaccine antigens. We investigated whether these CIAs are capable of promoting the immune response to Gardasil. Balb/c mice were immunized intramuscularly twice three weeks apart with 1/20 human dose of Gardasil alone or in combination with CIA02, CIA05 or both, and immune responses were assessed. The serum anti-HPV16 L1 VLP IgG antibody titer was significantly higher in mice administered CIA05 or CIA05 plus CIA02, but not in those given CIA02, compared with mice given Gardasil alone. A secreted alkaline phosphatase (SEAP)-based pseudovirus neutralization assay showed increased neutralizing antibody titers in both CIA05 and CIA05 plus CIA02 groups. Coadministration of CIA05 with Gardasil led to a marked increase in serum IgG2a antibody titer and the percentage of interferon (IFN)-gamma(+) cells in the spleen, indicating that CIA05 effectively promotes Th1-type immune responses. These data indicate that CIA05, in synergy with alum, enhances the immune response to HPV L1 VLPs and suggest its potential as an adjuvant for the development of a potent prophylactic HPV vaccine.
Han
Ji Eun
JE
Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea.
Kim
Hye Kyeong
HK
Park
Shin Ae
SA
Lee
Seung Jae
SJ
Kim
Hyoung Jin
HJ
Son
Ga Hyun
GH
Kim
Young Tae
YT
Cho
Yang Je
YJ
Kim
Hong-Jin
HJ
Lee
Na Gyong
NG
D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002213:Capsid / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D008070:Lipopolysaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053918:Papillomavirus Vaccines / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D008070:Lipopolysaccharides; D053918:Papillomavirus Vaccines