Abstract
BackgroundVaccination remains one of the most effective approaches to prevent the spread of infectious diseases. Immune responses to vaccination can be enhanced by inclusion of adjuvant in a vaccine. Paclitaxel extracted from the bark of the Pacific yew tree Taxus brevifola was previously demonstrated to have adjuvant property. Compared to paclitaxel, docetaxel is another member of taxane family, and is more soluble in water and easier to manipulate in medication. To investigate the adjuvant effect of this compound, we measured the immune responses induced by co-administration of a split inactivated influenza H1N1 vaccine antigen with docetaxel.ResultsWhen co-administered with docetaxel, lower dose antigen (equivalent to 10 ng HA) induced similar levels of IgG and IgG isotypes as well as HI titers to those induced by higher dose antigen (equivalent to 100 ng HA). Docetaxel promoted splenocyte responses to H1N1 antigen, ConA and LPS, mRNA expressions of cytokines (IFN-gamma, IL-12, IL-4 and IL-10) and T-bet/GATA-3 by splenocytes. The enhanced immunity was associated with up-expressed microRNAs (miR-155, miR-150 and miR-146a) in docetaxel-stimulated RAW264.7 cells. Docetaxel promoted similar IgE level to but alum promoted significantly higher IgE level than the control.ConclusionDocetaxel has adjuvant effect on the influenza H1N1 vaccine by up-regulation of Th1/Th2 immune responses. Considering its unique vaccine adjuvant property as well as the safe record as an anti-neoplastic agent clinically used in humans during a long period, docetaxel should be further studied for its use in influenza vaccine production.
Highlights
Vaccination remains one of the most effective approaches to prevent the spread of infectious diseases
The IgG titer induced by 10 ng HA in combination with docetaxel (100 or 200 μg) was 23 times higher than that induced by the same amount of HA (P < 0.01) and similar to the IgG titer elicited by 100 ng of HA (P > 0.05)
IgG titers were dose-dependent on the amount of docetaxel, and reached the highest when docetaxel was at 100 and 200 μg but was not significantly increased when docetaxel increased from 100 μg to 200 μg
Summary
Vaccination remains one of the most effective approaches to prevent the spread of infectious diseases. To investigate the adjuvant effect of this compound, we measured the immune responses induced by co-administration of a split inactivated influenza H1N1 vaccine antigen with docetaxel. The method has been utilized for many years, vaccination remains one of the most effective approaches, to prevent the spread of the influenza virus and to mitigate the severity of illness and the impact of the disease [3] Since the rapid spread of the swine-origin influenza A (H1N1) 2009 pandemic worldwide, the rapid implementation of a vaccine has become a global priority. The lack of cross-protective immunity between the pandemic and seasonal influenza virus strains highlighted the urgency of rapid vaccine development. The present global production capacity of trivalent seasonal influenza vaccine is about 876 million doses per year. In spite of the WHO global pandemic influenza action plan to increase the potential supply of pandemic influenza vaccine [5], the production of sufficient pandemic vaccine to immunize the world’s population would significantly exceed the existing manufacturing capacities
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