PDF(Pubmed)
Abstract：
Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, which are considered to be sufficient to protect against viral infection. Moreover, SARS-CoV-2 M2SR elicited cross-reactive serum and mucosal antibodies to the Omicron BA.4/BA.5 variant. The SARS-CoV-2 M2SR vaccine also maintained strong immune responses to influenza A with high titers of anti H3 serum IgG and hemagglutination inhibition (HAI) antibody titers corresponding to those seen from the control M2SR vector alone. With a proven safety record and robust immunological profile in humans that includes mucosal immunity, the M2SR influenza viral vector expressing key SARS-CoV-2 antigens could provide more efficient protection against influenza and SARS-CoV-2 variants.
摘要：
目前的SARS-CoV-2疫苗为COVID-19相关的住院和死亡提供保护，但在抑制初始感染和传播方面仍然效率低下。尽管更新了助推器配方，新出现的SARS-CoV-2变种的突破性感染和再感染很常见。鼻内接种以引起感染部位的粘膜免疫可以改善呼吸道病毒疫苗的性能。我们开发了SARS-CoV-2M2SR，SARS-CoV-2和流感疫苗的双重候选，使用我们的活的鼻内M2缺陷型单复制（M2SR）流感载体，表达原型菌株的SARS-CoV-2刺突蛋白的受体结合域（RBD），首次报道于2020年1月。用这种双重疫苗对小鼠的鼻内接种引起对RBD的高血清IgG和粘膜IgA滴度。接种小鼠的血清显示，接种疫苗的小鼠产生了针对原型和Delta病毒株的中和SARS-CoV-2抗体滴度，被认为足以防止病毒感染。此外，SARS-CoV-2M2SR引起了对OmicronBA.4/BA.5变体的交叉反应性血清和粘膜抗体。SARS-CoV-2M2SR疫苗还维持了对甲型流感的强免疫应答,具有高滴度的抗H3血清IgG和血凝抑制(HAI)抗体滴度,其对应于单独从对照M2SR载体观察到的那些。在人类中具有可靠的安全记录和强大的免疫学特征，包括粘膜免疫，表达关键SARS-CoV-2抗原的M2SR流感病毒载体可以提供更有效的针对流感和SARS-CoV-2变体的保护。
