Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7
AbstractQb 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. View Full-Text
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Akache, B.; Weeratna, R.D.; Deora, A.; Thorn, J.M.; Champion, B.; Merson, J.R.; Davis, H.L.; McCluskie, M.J. Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7. Vaccines 2016, 4, 3.
Akache B, Weeratna RD, Deora A, Thorn JM, Champion B, Merson JR, Davis HL, McCluskie MJ. Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7. Vaccines. 2016; 4(1):3.Chicago/Turabian Style
Akache, Bassel; Weeratna, Risini D.; Deora, Aparna; Thorn, Jennifer M.; Champion, Brian; Merson, James R.; Davis, Heather L.; McCluskie, Michael J. 2016. "Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7." Vaccines 4, no. 1: 3.
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