Abstract
During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 μg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 μg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.
Keywords: SARS-CoV-2; SWE; adjuvant; vaccine.
【저자키워드】 SARS-CoV-2, vaccine., adjuvant, SWE, 【초록키워드】 neutralizing antibody, viral infection, Efficacy, Vaccine, vaccination, immunogenicity, Mutation, Immunity, Neutralizing antibodies, Cellular immune response, COVID-19 pandemic, Antibody Response, T-cells, variant, Infection, B cells, Delta, viral spread, variants, binding affinity, Antigen, B cell, Viral, mice, herd immunity, immune responses, low dose, Lineage, Germinal center, Beta, Subunit vaccine, adjuvant, humoral immune response, T-cell, utility, rodent, rodents, T-cell responses, Antisera, Protective, protein subunit vaccine, Tfh, Vaccinations, ACE2 binding, aluminum, alum, Safe, mass vaccination, Support, aluminum hydroxide, These data, hydroxide, live SARS-CoV-2, trimer, clinical testing, prefusion, lower dose, different doses, Complete, Prevent, effective, ENhance, produced, addition, evaluated, demonstrated, induce, comparable, feasible, sustained, exhibit, the antibody response, different dose, follicular, were assessed, 【제목키워드】 induced, Emulsion,