Data from: Nasal immunization with small molecule mast cell activators enhance immunity to co-administered subunit immunogens

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  • Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. However, small molecule mast cell activators may be a more cost-efficient adjuvant alternative that is easily synthesized with high purity compared to M7 or C48/80. To identify novel mast cell activating compounds that could be evaluated for mucosal vaccine adjuvant activity, we employed high-throughput screening to assess over 55,000 small molecules for mast cell degranulation activity. Fifteen mast cell activating compounds were down-selected to five compounds based on in vitro immune activation activities including cytokine production and cellular cytotoxicity, synthesis feasibility, and selection for functional diversity. These small molecule mast cell activators were evaluated for in vivo adjuvant activity and induction of protective immunity against West Nile Virus infection in BALB/c mice when combined with West Nile Virus envelope domain III (EDIII) protein in a nasal vaccine. We found that three of the five mast cell activators, ST101036, ST048871, and R529877, evoked high levels of EDIII-specific antibody and conferred comparable levels of protection against WNV challenge. The level of protection provided by these small molecule mast cell activators was comparable to the protection evoked by M7 (67%), but markedly higher than the levels seen with mice immunized with EDIII alone (no adjuvant 33%). Thus, novel small molecule mast cell activators identified by high throughput screening are as efficacious as previously described mast cell activators when used as nasal vaccine adjuvants and represent next generation mast cell activators for evaluation in mucosal vaccine studies ... [Read More]

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Data Citation
  • Johnson-Weaver, B., Choi, H. Yang, H., Granek, J., Chan, C. Abraham, S. & Staats, H. (2021). Data from: Nasal immunization with small molecule mast cell activators enhance immunity to co-administered subunit immunogens. Duke Research Data Repository. https://doi.org/10.7924/r4h133m7w
DOI
  • 10.7924/r4h133m7w
Publication Date
ARK
  • ark:/87924/r4h133m7w
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Related Materials
  • Johnson-Weaver, B. T., Choi, H. W., Yang, H., Granek, J. A., Chan, C., Abraham, S. N., & Staats, H. F. (2021). Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens. Frontiers in immunology, 12, 730346.  https://doi.org/10.3389/fimmu.2021.730346
Funding Agency
  • National Institute of Allergy and Infectious Diseases (NIAID)
Grant Number
  • Adjuvant Discovery Contract #HHSN272201400054C
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Title
  • Data from: Nasal immunization with small molecule mast cell activators enhance immunity to co-administered subunit immunogens
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Thumbnail Title Date Uploaded Visibility Actions
file details Mast Cell Activator Adjuvant Readme.txt 2021-09-03 Public Download
file details Mast cell activator_Data summary_submitted.xlsx 2021-09-03 Public Download
file details Mast cell activator_Data summary_submitted.xml 2021-09-03 Public Download

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