In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 6, No. 61 ( 2021-07-29)
Abstract:
Ongoing severe acute respiratory syndrome coronavirus–2 (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 adjuvant. The RBD + 3M-052-alum–adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved T H 1-biased CD4 + T cell reactions, and increased CD8 + T cell responses when compared with the alum-alone adjuvanted vaccine. RBD + 3M-052-alum induced a significant reduction of SARS-CoV-2 virus in the 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 bronchoalveolar lavage (BAL). RBD + 3M-052-alum blocked a post–SARS-CoV-2 challenge increase in CD14 + CD16 ++ intermediate blood monocytes, and fractalkine, MCP-1 (monocyte chemotactic protein–1), and TRAIL (tumor necrosis factor–related apoptosis-inducing ligand) in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Last, 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.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abh3634
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2021
detail.hit.zdb_id:
2862556-0
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