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.

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ALVAC-induced CREB1 activity predicts reduced HIV-1 infection.To define the immune mechanisms triggered by ALVAC priming in Study 36 (schematic in Extended Data Fig. 1a), transcriptional profiling of purified DCs, CD4 + T cells and B cells was performed at pre-vaccination, and days 2/3, week 2 and week 25 post initial vaccination in NHPs immunized with ALVAC-HIV-1 (G2) or empty ALVAC (G1). The sample collection and analytical

Rheumatoid arthritis an autoimmune infectious disorder, is categorized by in ammation and increased level of pro-in ammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic in ammation. On the basis of established anti-in ammatory e cacy of Nerolidol, the primary study was further appraised to determine its e cacy against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was persuaded by inoculation of 0.1mL CFA injection into left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radio-graphics of ankle joints. Expressions of cytokine's panels like IL-10, IL-4, COX-2, NF-K β, TNF-α, IL-6, PGE-2 and IL-1β were determined by real time qPCR. Antioxidant enzyme analyses was calculated by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented the body weight loss, stabilized the biochemical and haematological homeostasis and signi cantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, over expression of gene pointers like TNF-α, IL-1β, IL-6, NF-K β, PGE-2 and COX-2 in CFA treated control rats were also reversed with nerolidol. This antiarthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum anti-oxidant activity. The present ndings demonstrate that nerolidol reduce the adjuvant arthritis by down-regulating the proin ammatory cytokines and up-regulating the aforementioned anti-in ammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.