Dalvie, Neil C.Tostanoski, Lisa H.Rodriguez-Aponte, Sergio A.Kaur, KawaljitBajoria, SakshiKumru, Ozan S.Martinot, Amanda J.Chandrashekar, AbishekMcMahan, KatherineMercado, Noe B.Yu, JingyouChang, AiquanGiffin, Victoria M.Nampanya, FelixPatel, ShivaniBowman, LesleyNaranjo, Christopher A.Yun, DongsooFlinchbaugh, ZachPessaint, LaurentBrown, RenitaVelasco, JasonTeow, ElyseCook, AnthonyAndersen, HanneLewis, Mark G.Camp, Danielle L.Silverman, Judith MaxwellNagar, Gaurav S.Rao, Harish D.Lothe, Rakesh R.Chandrasekharan, RahulRajurkar, Meghraj P.Shaligram, Umesh S.Kleanthous, HarryJoshi, Sangeeta B.Volkin, David B.Biswas, SumiLove, J. ChristopherBarouch, Dan H.2022-04-282022-04-282022-03-16Dalvie, N. C., Tostanoski, L. H., Rodriguez-Aponte, S. A., Kaur, K., Bajoria, S., Kumru, O. S., Martinot, A. J., Chandrashekar, A., McMahan, K., Mercado, N. B., Yu, J., Chang, A., Giffin, V. M., Nampanya, F., Patel, S., Bowman, L., Naranjo, C. A., Yun, D., Flinchbaugh, Z., Pessaint, L., … Barouch, D. H. (2022). SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques. Science advances, 8(11), eabl6015. https://doi.org/10.1126/sciadv.abl6015https://hdl.handle.net/1808/32725Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain–hepatitis B surface antigen virus–like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>104) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log10) and nasal mucosa (~2.9 log10) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.Copyright © 2022. The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).http://creativecommons.org/licenses/by/4.0/Article10.1126/sciadv.abl6015https://orcid.org/ 0000-0002-7912-0309https://orcid.org/ 0000-0001-9255-5684https://orcid.org/ 0000-0002-6271-7918https://orcid.org/ 0000-0003-2624-9755https://orcid.org/ 0000-0001-8782-0842https://orcid.org/ 0000-0002-5010-7223https://orcid.org/ 0000-0001-6237-6191https://orcid.org/ 0000-0001-7821-5552https://orcid.org/ 0000-0002-3933-0539https://orcid.org/ 0000-0001-7769-7326https://orcid.org/ 0000-0002-0775-6623https://orcid.org/ 0000-0002-9482-0979https://orcid.org/ 0000-0002-9783-302Xhttps://orcid.org/ 0000-0003-4102-1265https://orcid.org/ 0000-0003-3475-1016https://orcid.org/ 0000-0001-6838-7174https://orcid.org/ 0000-0002-2126-3008https://orcid.org/ 0000-0003-1103-9608https://orcid.org/ 0000-0001-7852-0135https://orcid.org/ 0000-0001-8299-7155https://orcid.org/ 0000-0001-7115-235Xhttps://orcid.org/ 0000-0003-0921-3144https://orcid.org/ 0000-0001-5127-4659openAccess