ABSTRACT
Messenger RNA (mRNA, mRNA) vaccines and antibodies are a new type of vaccine and antibody technology emerging in recent years. Compared with traditional vaccines, mRNA vaccines have the advantages of high safety, good balanced immunity, short development cycle, and low production costs. mRNA antibodies exert biological effects in vivo earlier and longer than other forms of delivered antibodies. With the rapid development of mRNA modification and delivery technology, mRNA technology is rapidly maturing, showing broad application prospects in tumor treatment, prevention and treatment of viral infectious diseases, etc. In particular, the new coronavirus mRNA vaccine has been completed at a record speed The development and successful application paves the way for the promotion of mRNA technology in the future. This paper reviews the important breakthroughs in the field of mRNA technology, focusing on the major progress of mRNA vaccines and antibodies in response to viral infectious diseases, and looks forward to the future research trends of this technology in the field of anti-viral infection.
ABSTRACT
The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the still ravaging COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Significantly, both antibodies confer good mutation resistance to the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics, and can also inform the design of pan-sarbecovirus vaccines.
Subject(s)
COVID-19ABSTRACT
Background: Knowledge of host immune response after natural SARS-CoV-2 infection is essential for the direction of vaccination and epidemiological control strategies against COVID-19. Methods: : Thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. Results: : IgG titers reached a peak later (35 days postonset) than those of Nab, Ab, IgM and IgA (25 days postonset). IgM levels declined with an estimated half-life of 35 days postonset, which was more rapid than those of IgA and IgG (73-76 days postonset). All patients remained positive for NAb, IgG and IgA up to 3 months after illness onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized β regression coefficient: 0.53 vs 0.48). However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. Conclusions: : This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients. Humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.
Subject(s)
COVID-19ABSTRACT
Knowledge of the host immune response after natural SARS-CoV-2 infection is essential for informing directions of vaccination and epidemiological control strategies against COVID-19. In this study, thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. IgG titers reached a peak later (approximately 35 days postonset) than those of Nab, Ab, IgM and IgA (20~25 days postonset). After peaking, IgM levels declined with an estimated average half-life of 10.36 days, which was more rapid than those of IgA (51.25 days) and IgG (177.39 days). Based on these half-life data, we estimate that the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized {beta} regression coefficient: 0.53 vs 0.48), so the rapid decline in NAb may be attributed to the rapid decay of IgM in acute phase. However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. It's assumed that the decline rate of NAb might slow down to the same level as that of IgG over time. This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients and that humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.
Subject(s)
COVID-19ABSTRACT
To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 M.