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Vaccination is a cost‐effective medical intervention. Inactivated whole virusor large protein fragments‐based severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi‐source data integrated linear B‐cell epitope screening strategy is presented and a linear B‐cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose‐dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS‐CoV‐2 wild‐type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain‐freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS‐CoV‐2 wild‐type strain as demonstrated by live SARS‐CoV‐2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B‐cell epitope‐based vaccines against SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Background: To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID‐19 for an efficacy study; herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults. Methods: These randomized, double‐blind, placebo‐controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 μg vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo. Results: No serious vaccine‐related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS‐CoV‐2. The vaccine induced significant neutralizing antibody responses to live SARS‐CoV‐2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 μg doses, respectively; the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic. [ABSTRACT FROM AUTHOR]

In comparation with antibody titers induced by RBD/351 and RBD/131, the neutralizing antibody titers induced by RBD/617 have two to threefold increase. RBD alone were used as the antigen to avoid the antibody-dependent enhancement,[4] but RBD is not as immunogenic as the whole S protein or the whole virus vaccine. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel subset of coronavirus that causes coronavirus disease 2019 (COVID-19), but vaccine development is hampered by the high mutation of virus. [Extracted from the article]

To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus. [ABSTRACT FROM AUTHOR]