| Autor: |
Pino, Maria, Abid, Talha, Pereira Ribeiro, Susan, Edara, Venkata Viswanadh, Floyd, Katharine, Smith, Justin C., Latif, Muhammad Bilal, Pacheco-Sanchez, Gabriela, Dutta, Debashis, Wang, Shelly, Gumber, Sanjeev, Kirejczyk, Shannon, Cohen, Joyce, Stammen, Rachelle L., Jean, Sherrie M., Wood, Jennifer S., Connor-Stroud, Fawn, Pollet, Jeroen, Chen, Wen-Hsiang, Wei, Junfei |
| Zdroj: |
Science Immunology; 2021, Vol. 6 Issue 61, p1-18, 18p |
| Abstrakt: |
Adjuvant adds protection to COVID-19 vaccine: Despite vaccinations against severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) being rolled out globally, it is important to consider the next generation of SARS-CoV-2 vaccines and adjuvants that might increase protection. Here, Pino et al. vaccinated rhesus macaques (RM) with a yeast-expressed RBD-based SARS-CoV-2 vaccine adjuvanted with 3M-052 (TLR7/8 agonist)–alum, previously shown to induce better immune responses against human immunodeficiency virus. Comparing this RBD-based vaccine adjuvanted with 3M-052-alum to the one adjuvanted only with alum, RMs were more protected from a SARS-CoV-2 challenge. This amplified protection correlated to increased SARS-CoV-2–specific antibody and T cell responses in the blood and the nasal mucosa. Thus, using the adjuvant 3M-052-alum may be a way to improve the efficacy of SARS-CoV-2 vaccines moving forward. 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 TH1-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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