title: Effect of alternative aluminum adjuvants on the absorption and immunogenicity of HPV16 L1 VLPs in mice.
abstract: Aluminum adjuvants are commonly used in prophylactic vaccines to enhance antigen immunogenicity through induction of high-titer antibody responses. Three major forms of aluminum adjuvants with substantially different physical and chemical properties have been described: aluminum phosphate (AlPO(4)), aluminum hydroxide (AlOH) and amorphous aluminum hydroxyphosphate sulfate (AAHS). Here we describe the effect of these different aluminum adjuvants on the formulation and subsequent immunogenicity in mice of virus-like particles (VLPs) consisting of the L1 protein of Human Papillomavirus (HPV) Type 16. Electron microscopy demonstrated that the physical appearance of the phosphate-containing aluminum adjuvants was markedly different from that of aluminum hydroxide. All three aluminum adjuvants were found to display unique surface charge profiles over a range of pH, while AAHS demonstrated the greatest inherent capacity for adsorption of L1 VLPs. These differences were associated with differences in immunogenicity: anti-HPV L1 VLP responses from mice immunized with AAHS-formulated HPV16 vaccine were substantially greater than those produced by mice immunized with the same antigen formulated with aluminum hydroxide. In addition, HPV L1 VLPs formulated on AAHS also induced a substantial interferon-gamma secreting T cell response to L1 peptides indicating the potential for an enhanced memory response to this antigen. These results indicate that the chemical composition of aluminum adjuvants can have a profound influence on the magnitude and quality of the immune response to HPV VLP vaccines.
authors.affiliation: Vaccine & Biologics Research, Merck Research Laboratories, West Point, Pennsylvania 19846, USA. michael_caufield@merck.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caulfield
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Tobery
authors.forename: Henryck
authors.initials: H
authors.lastname: Mach
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Ahl
authors.forename: Jayme L
authors.initials: JL
authors.lastname: Cannon
authors.forename: James C
authors.initials: JC
authors.lastname: Cook
authors.forename: Jon H
authors.initials: JH
authors.lastname: Heinrichs
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sitrin
mesh_terms: D000042:Absorption / Q000187:drug effects; D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D036022:Capsid Proteins / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D010710:Phosphates / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D010710:Phosphates; D000536:Aluminum Hydroxide; C063317:L1 protein, Human papillomavirus type 16; D007371:Interferon-gamma; C524363:aluminum hydroxyphosphate sulfate; C012714:aluminum phosphate