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bioRxiv · 10.1101/2022.01.04.474916

S100A4 exerts robust mucosal adjuvant activity for co-administered antigens in mice

Sen Chaudhuri, A.·Yeh, Y.-W.·Sun, J.-B.·Zewdie, O.·Jin, T.·Wei, B.·Holmgren, J.·Zou, X.
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Abstract

The lack of clinically applicable mucosal adjuvants is a major hurdle in designing effective mucosal vaccines. We hereby report that the calcium-binding protein S100A4, which regulates a wide range of biological functions, is a potent mucosal adjuvant in mice for co-administered antigens, including the SARS-CoV-2 spike protein, with comparable or even superior efficacy as cholera toxin but without causing any adverse reactions. Intranasal immunization with recombinant S100A4 elicited antigen-specific antibody and pulmonary cytotoxic T cell responses, and these responses were remarkably sustained for longer than six months. As a self-protein, S100A4 did not stimulate antibody responses against itself, a quality desired of adjuvants. S100A4 prolonged nasal residence of intranasally delivered antigens and promoted migration of antigen-presenting cells. S100A4-pulsed dendritic cells potently activated cognate T cells. Furthermore, S100A4 induced strong germinal center responses revealed by both microscopy and mass spectrometry, a novel technique for measuring germinal center activity. In conclusion, S100A4 may be a promising adjuvant in formulating mucosal vaccines, including vaccines against pathogens that infect via the respiratory tract, such as SARS-CoV-2.

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Sen Chaudhuri, A., Yeh, Y.-W., Sun, J.-B., Zewdie, O., Jin, T., Wei, B., Holmgren, J., Zou, X.. 2022-01-04. S100A4 exerts robust mucosal adjuvant activity for co-administered antigens in mice. https://doi.org/10.1101/2022.01.04.474916

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