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Vaccines 2016, 4(1), 3; doi:10.3390/vaccines4010003

Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7

1
Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, 340 Terry Fox Drive, suite 200, Ottawa, ON K2K 3A2, Canada
2
Pfizer Biotherapeutics Pharmaceutical Sciences, St. Louis, MO 63017, USA
3
Pfizer Vaccine Immunotherapeutics, La Jolla, CA 92121, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Diane M. Harper
Received: 7 December 2015 / Revised: 15 January 2016 / Accepted: 19 January 2016 / Published: 21 January 2016
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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. View Full-Text
Keywords: Qb; VLP; TLR7; bacteriophage; IgE; asthma; CpG Qb; VLP; TLR7; bacteriophage; IgE; asthma; CpG
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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.

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