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Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.

Publication ,  Journal Article
Johnson-Weaver, BT; Choi, HW; Yang, H; Granek, JA; Chan, C; Abraham, SN; Staats, HF
Published in: Front Immunol
2021

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.

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Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2021

Volume

12

Start / End Page

730346

Location

Switzerland

Related Subject Headings

  • West Nile virus
  • West Nile Virus Vaccines
  • West Nile Fever
  • Proof of Concept Study
  • Mice, Inbred BALB C
  • Mice
  • Mast Cells
  • Immunogenicity, Vaccine
  • Immunization
  • Immunity, Mucosal
 

Citation

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MLA
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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. Front Immunol, 12, 730346. https://doi.org/10.3389/fimmu.2021.730346
Johnson-Weaver, Brandi T., Hae Woong Choi, Hang Yang, Josh A. Granek, Cliburn Chan, Soman N. Abraham, and Herman F. Staats. “Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.Front Immunol 12 (2021): 730346. https://doi.org/10.3389/fimmu.2021.730346.
Johnson-Weaver BT, Choi HW, Yang H, Granek JA, Chan C, Abraham SN, et al. Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens. Front Immunol. 2021;12:730346.
Johnson-Weaver, Brandi T., et al. “Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.Front Immunol, vol. 12, 2021, p. 730346. Pubmed, doi:10.3389/fimmu.2021.730346.
Johnson-Weaver BT, Choi HW, Yang H, Granek JA, Chan C, Abraham SN, Staats HF. Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens. Front Immunol. 2021;12:730346.

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2021

Volume

12

Start / End Page

730346

Location

Switzerland

Related Subject Headings

  • West Nile virus
  • West Nile Virus Vaccines
  • West Nile Fever
  • Proof of Concept Study
  • Mice, Inbred BALB C
  • Mice
  • Mast Cells
  • Immunogenicity, Vaccine
  • Immunization
  • Immunity, Mucosal