@article{a338ce5ec0174ef4b4669e2ef93a973b,
title = "Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques",
abstract = "Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.",
keywords = "Adjuvant, Macaque, Nanoparticle, SARS-CoV-2, Vaccine",
author = "King, {Hannah A.D.} and {Gordon Joyce}, M. and Ines Lakhal-Naouar and Aslaa Ahmed and Cincotta, {Camila Macedo} and Caroline Subra and Peachman, {Kristina K.} and Hack, {Holly R.} and Chen, {Rita E.} and Thomas, {Paul V.} and Chen, {Wei Hung} and Sankhala, {Rajeshwer S.} and Agnes Hajduczki and Martinez, {Elizabeth J.} and Peterson, {Caroline E.} and Chang, {William C.} and Misook Choe and Clayton Smith and Headley, {Jarrett A.} and Elyard, {Hanne A.} and Anthony Cook and Alexander Anderson and {McGuckin Wuertz}, Kathryn and Ming Dong and Isabella Swafford and Case, {James B.} and Currier, {Jeffrey R.} and Lal, {Kerri G.} and Amare, {Mihret F.} and Vincent Dussupt and Sebastian Molnar and Daye, {Sharon P.} and Xiankun Zeng and Barkei, {Erica K.} and Kendra Alfson and Staples, {Hilary M.} and Ricardo Carrion and Krebs, {Shelly J.} and Dominic Paquin-Proulx and Nicos Karasavvas and Polonis, {Victoria R.} and Jagodzinski, {Linda L.} and Sandhya Vasan and Scott, {Paul T.} and Yaoxing Huang and Nair, {Manoj S.} and Ho, {David D.} and {de Val}, Natalia and Diamond, {Michael S.} and Lewis, {Mark G.} and Mangala Rao and Matyas, {Gary R.} and Gromowski, {Gregory D.} and Peel, {Sheila A.} and Michael, {Nelson L.} and Kayvon Modjarrad and Bolton, {Diane L.}",
note = "Funding Information: Author contributions: H.A.D.K., M.G.J., R.C.J., S.V., P.T.S., N.L.M., K.M., and D.L.B. designed research; H.A.D.K., M.G.J., I.L.-N., A. Ahmed, C.M.C., C. Subra, K.K.P., H.H.H., R.E.C., P.V.T., W.-H.C., R.S.S., A.H., E.J.M., C.E.P., W.C.C., M.C., C. Smith, H.A.E., A.C., K.M.W., M.D., I.S., J.B.C., J.R.C., K.G.L., V.D., S.M., S.P.D., X.Z., E.K.B., K.A., H.M.S., R.C.J., S.J.K., D.P.-P., N.K., V.R.P., L.L.J., Y.H., M.S.N., N.d.V., M.G.L., G.D.G., and D.L.B. performed research; A. Anderson, J.R.C., M.R., and G.R.M. contributed new reagents/analytic tools; H.A.D.K., I.L.-N., A. Ahmed, C.M.C., C. Subra, K.K.P., H.H.H., R.E.C., J.A.H., I.S., M.F.A., X.Z., E.K.B., K.A., H.M.S., S.J.K., D.P.-P., N.K., L.L.J., Y.H., M.S.N., D.D.H., M.S.D., M.R., G.D.G., S.A.P., and D.L.B. analyzed data; and H.A.D.K., K.M., and D.L.B. wrote the paper. Competing interest statement: M.G.J. and K.M. are named as inventors on International Patent Application no. WO/2021/21405 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” M.G.J. is named as an inventor on International Patent Application no. WO/2018/081318 entitled “Prefusion Coronavirus Spike Proteins and Their Use.” M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The M.S.D. laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. This article is a PNAS Direct Submission. Funding Information: ACKNOWLEDGMENTS. We thank M. Taddese, J. Lay, E. Zografos, J. Lynch, L. Mendez-Rivera, N. Jackson, J. Headley, M. Amare, B. Slike, U. Tran, P. J. Lee, S. Padilla, H. Hernandez, D. Coleman, H. Groove, R. J. O{\textquoteright}Connell, J. Bolton, T. Robinson, E. Duncan, and H. Siegfried for technical support, assistance, and advice. We thank C. Alving and Z. Beck for designing the adjuvant. We acknowledge support from the US Department of Defense, Defense Health Agency (Restoral FY20), and NIH grant (R01 AI157155). This work was also partially executed through a cooperative agreement between the US Department of Defense and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (W81XWH-18-2-0040) and was supported, in part, by the US Army Medical Research and Development Command under Contract W81-XWH-18-C-0337. The views, opinions, and/or findings are those of the authors and should not be construed to represent the positions, policy, or decision of the US Army or the Department of Defense. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",
year = "2021",
month = sep,
day = "21",
doi = "10.1073/pnas.2106433118",
language = "English",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "38",
}