Abstract
Traditional non-living vaccines are often least effective in the populations that need them most, such as neonates and elderly adults. Vaccine adjuvants are one approach to boost the immunogenicity of antigens in populations with reduced immunity. Ideally, vaccine adjuvants will increase the seroconversion rates across the population, lead to stronger immune responses, and enable the administration of fewer vaccine doses. We previously demonstrated that a cationic liposomal formulation of the commercial influenza split virus vaccine (CCS/C-HA) enhanced cellular and humoral immunity to the virus, increased seroconversion rates, and improved survival after live virus challenge in a preclinical model, as compared to the commercial vaccine as is (F-HA). We now evaluated vaccine efficacy in different strains and sexes of mice and determined the role of innate immunity in the mechanism of action of the CCS/C adjuvant by testing the response of mice deficient in Toll-like receptors or the TLR/IL-1 adaptor protein MyD88 following immunization with CCS/C-HA vs. F-HA. Although TLR2- and TLR4-deficient mice responded to F-HA immunization, F-HA immunization failed to engender a significant immune response in the absence of MyD88. In contrast, immunization with the CCS/C-HA vaccine overcame the requirement for MyD88 in the response to the commercial vaccine and improved the immune responses and seroconversion rates in all strains of mice tested, including those deficient in TLR2 and TLR4.
Original language | American English |
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Pages (from-to) | 3146-3154 |
Number of pages | 9 |
Journal | Human Vaccines and Immunotherapeutics |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - 2020 |
Bibliographical note
Funding Information:This work was supported by the Israel Science Foundation (grants 1396/12 and 1391/17), and by the Barenholz Research Fund (the Barenholz Research Fund was established by Professor Barenholz from royalties obtained from various Barenholz licensed patents, and these funds are dedicated to support research in the Barenholz Lab). OE was supported by a Hebrew University scholarship for outstanding students.
Publisher Copyright:
© 2020 Taylor & Francis Group, LLC.
Keywords
- Influenza
- MyD88
- TLR
- adjuvant
- cationic liposomes