@article{636e3986711e4e09a288927f902c933e,
title = "Increased vaccine tolerability and protection via NF-kB modulation",
abstract = "Improving adjuvant responses is a promising pathway to develop vaccines against some pathogens (e.g., HIV or dengue). One challenge in adjuvant development is modulating the inflammatory response, which can cause excess side effects, while maintaining immune activation and protection. No approved adjuvants yet have the capability to independently modulate inflammation and protection. Here, we demonstrate a method to limit inflammation while retaining and often increasing the protective responses. To accomplish this goal, we combined a partial selective nuclear factor kappa B (NF-kB) inhibitor with several current adjuvants. The resulting vaccines reduce systemic inflammation and boost protective responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method was tested across a broad range of adjuvants and antigens. We anticipate these studies will lead to an alternative approach to vaccine formulation design that may prove broadly applicable to a wide range of adjuvants and vaccines.",
author = "Moser, {B. A.} and Steinhardt, {R. C.} and Y. Escalante-Buendia and Boltz, {D. A.} and Barker, {K. M.} and Cassaidy, {B. J.} and Rosenberger, {M. G.} and S. Yoo and McGonnigal, {B. G.} and Esser-Kahn, {A. P.}",
note = "Funding Information: Acknowledgments: We thank A. Burkhardt and A. Gilkes for training and assistance with in vivo techniques. We thank R. Nakajima for assistance with imaging microarrays and D. Piraner for help with image analysis. We thank A. Chon for assistance with HPLC optimization and N. Nihesh for training and assistance with peptide synthesis. We acknowledge J. Qin at the University of Chicago for training and assistance with mass spectrometry. Funding: We would like to acknowledge support by the NIH (1U01Al124286-01 and 1DP2Al112194-01, GM099594). This work was supported by the Defense Threat Reduction Agency (DTRA) under contract supporting this work (HDTRA11810052). A.P.E.-K. thanks the Pew Scholars Program and the Cottrell Scholars Program for support. B.A.M. thanks NSF-GRFP (DGE-1321846), and B.J.C. thanks NSF-GRFP (DGE-1746045). We would like to thank NSF instrumentation grant CHE-1048528. This work was supported, in part, by a grant from the Alfred P. Sloan Foundation. Author contributions: B.A.M. and A.P.E.-K. conceived of and designed the project and experiments and wrote the manuscript. B.A.M., R.C.S., Y.E.-B., D.A.B., K.M.B., and B.G.M. performed the experiments. B.A.M., B.J.C., M.G.R., and S.Y. synthesized materials. Competing interests: B.A.M. and A.E.K. are inventors on a pending patent related to this work filed by the University of Chicago (no. PCT/US19/64888, filed 16 December 2019). The authors declare that they have no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors. Publisher Copyright: {\textcopyright} 2020 The Authors, some rights reserved.",
year = "2020",
month = sep,
doi = "10.1126/sciadv.aaz8700",
language = "English (US)",
volume = "6",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "37",
}