title: Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7.
abstract: Qb bacteriophage virus-like particles (Qb-VLP) are utilized as carriers to enhance immune responses to weakly or non-immunogenic antigens such as peptides and haptens. Qb-VLPs are formed through the self-assembly of multiple Qb capsid protein monomers, a process which traps a large amount of bacterial RNA in the core of the VLP. Bacterial RNA is known to activate the innate immune system via TLR 7 and 8 found within the endosomes of certain immune cells and has been shown to contribute to the immunogenicity of Qb-VLP vaccines. Herein, we evaluated an anti-IgE vaccine comprised of two IgE peptides (Y and P) conjugated to Qb-VLP (Qb-Y and Qb-P, respectively) for in vitro stimulation of human PBMCs and in vivo immunogenicity in mice. The in vitro secretion of IFN-α from human PBMCs exposed to Qb-Y is consistent with TLR7 activation. Immunization of mice with the IgE peptide Qb-VLP conjugates induced high titers of anti-IgE antibodies in wild-type mice, but significantly lower titers in TLR7 knockout mice, supporting the self-adjuvanting role of the RNA. Inclusion of alum and alum/CpG as adjuvants partially or completely compensated for the lack of TLR7 activation in TLR7-deficient mice. Our study demonstrates the key role that TLR7 plays in the immunogenicity of the IgE peptide Qb-VLP conjugate vaccine.
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, 340 Terry Fox Drive, suite 200, Ottawa, ON K2K 3A2, Canada. bassel.akache@pfizer.com.
authors.forename: Bassel
authors.initials: B
authors.lastname: Akache
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, 340 Terry Fox Drive, suite 200, Ottawa, ON K2K 3A2, Canada. risini.weeratna@pfizer.com.
authors.forename: Risini D
authors.initials: RD
authors.lastname: Weeratna
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences, St. Louis, MO 63017, USA. aparna.deora@pfizer.com.
authors.forename: Aparna
authors.initials: A
authors.lastname: Deora
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences, St. Louis, MO 63017, USA. jennifer.thorn@pfizer.com.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Thorn
authors.affiliation: Pfizer Vaccine Immunotherapeutics, La Jolla, CA 92121, USA. brian.champion@psioxus.com.
authors.forename: Brian
authors.initials: B
authors.lastname: Champion
authors.affiliation: Pfizer Vaccine Immunotherapeutics, La Jolla, CA 92121, USA. james.merson@pfizer.com.
authors.forename: James R
authors.initials: JR
authors.lastname: Merson
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, 340 Terry Fox Drive, suite 200, Ottawa, ON K2K 3A2, Canada. heather.davis@pfizer.com.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, 340 Terry Fox Drive, suite 200, Ottawa, ON K2K 3A2, Canada. michael.mccluskie@pfizer.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCluskie
keywords: CpG; IgE; Qb; TLR7; VLP; asthma; bacteriophage