TY - JOUR
T1 - The cationic liposome CCS/C adjuvant induces immunity to influenza independently of the adaptor protein MyD88
AU - Even-Or, Orli
AU - Avniel-Polak, Shani
AU - Barenholz, Yechezkel
AU - Nussbaum, Gabriel
N1 - Publisher Copyright:
© 2020 Taylor & Francis Group, LLC.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Influenza
KW - MyD88
KW - TLR
KW - adjuvant
KW - cationic liposomes
UR - http://www.scopus.com/inward/record.url?scp=85085521881&partnerID=8YFLogxK
U2 - 10.1080/21645515.2020.1750247
DO - 10.1080/21645515.2020.1750247
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C2 - 32401698
AN - SCOPUS:85085521881
SN - 2164-5515
VL - 16
SP - 3146
EP - 3154
JO - Human Vaccines and Immunotherapeutics
JF - Human Vaccines and Immunotherapeutics
IS - 12
ER -