title: Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines.
abstract: Although glycoconjugate vaccines are generally very efficacious, there is still a need to improve their efficacy, especially in eliciting a strong primary antibody response. We have recently described a new type of vaccine adjuvant based on a TLR7 agonist adsorbed to alum (Alum-TLR7), which is highly efficacious at enhancing immunogenicity of protein based vaccines. Since no adjuvant has been shown to potentiate the immune response to glycoconjugate vaccines in humans, we investigated if Alum-TLR7 is able to improve immunogenicity of this class of vaccines. We found that in a mouse model Alum-TLR7 greatly improved potency of a CRM197-MenC vaccine increasing anti-MenC antibody titers and serum bactericidal activity (SBA) against MenC compared to alum adjuvanted vaccine, especially with a low dose of antigen and already after a single immunization. Alum-TLR7 also drives antibody response towards Th1 isotypes. This adjuvant was also able to increase immunogenicity of all polysaccharides of a multicomponent glycoconjugate vaccine CRM197-MenACWY. Furthermore, we found that Alum-TLR7 increases anti-polysaccharide immune response even in the presence of a prior immune response against the carrier protein. Finally, we demonstrate that Alum-TLR7 adjuvant effect requires a functional TLR7. Taken together, our data support the use of Alum-TLR7 as adjuvant for glycoconjugate vaccines.
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Buonsanti
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Balocchi
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Carole
authors.initials: C
authors.lastname: Harfouche
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Corrente
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Galli Stampino
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Tontini
authors.affiliation: GSK Vaccines, Cambridge, MA, USA.
authors.forename: Padma
authors.initials: P
authors.lastname: Malyala
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bufali
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Baudner
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: GSK Vaccines, Cambridge, MA, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Valiante
authors.affiliation: GSK Vaccines, Cambridge, MA, USA.
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: D'Oro
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D005260:Female; D006001:Glycoconjugates / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007074:Immunoglobulin G / Q000096:biosynthesis; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009345:Neisseria meningitidis / Q000187:drug effects / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000008:administration & dosage* / Q000737:chemistry; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D006001:Glycoconjugates; D007074:Immunoglobulin G; C525703:MenACWY; D022401:Meningococcal Vaccines; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin); D000536:Aluminum Hydroxide