A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates.

Journal Article (Journal Article)

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.

Full Text

Duke Authors

Cited Authors

  • Pino, M; Abid, T; Pereira Ribeiro, S; Edara, VV; Floyd, K; Smith, JC; Latif, MB; Pacheco-Sanchez, G; Dutta, D; Wang, S; Gumber, S; Kirejczyk, S; Cohen, J; Stammen, RL; Jean, SM; Wood, JS; Connor-Stroud, F; Pollet, J; Chen, W-H; Wei, J; Zhan, B; Lee, J; Liu, Z; Strych, U; Shenvi, N; Easley, K; Weiskopf, D; Sette, A; Pollara, J; Mielke, D; Gao, H; Eisel, N; LaBranche, CC; Shen, X; Ferrari, G; Tomaras, GD; Montefiori, DC; Sekaly, RP; Vanderford, TH; Tomai, MA; Fox, CB; Suthar, MS; Kozlowski, PA; Hotez, PJ; Paiardini, M; Bottazzi, ME; Kasturi, SP

Published Date

  • July 15, 2021

Published In

Volume / Issue

  • 6 / 61

PubMed ID

  • 34266981

Pubmed Central ID

  • PMC9119307

Electronic International Standard Serial Number (EISSN)

  • 2470-9468

Digital Object Identifier (DOI)

  • 10.1126/sciimmunol.abh3634

Language

  • eng

Conference Location

  • United States