目的　评价分别用Al(OH)₃、MF59、AS03和QS21佐剂配伍的新型冠状病毒（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）和流感病毒联合疫苗在小鼠中的免疫原性。方法　分别用Al(OH)₃、MF59、AS03和QS21佐剂配制SARS-CoV-2（灭活）和四价流感病毒（裂解）联合疫苗，在第0、14天分别腹腔注射免疫BALB/c小鼠，第14、28天采血检测血清抗SARS-CoV-2抗体滴度和流感血凝抑制滴度，并在第28天分离脾脏淋巴细胞检测针对SARS-CoV-2和流感病毒的细胞免疫应答。结果　不同佐剂的SARS-CoV-2和流感病毒联合疫苗均能诱导小鼠产生抗原特异性的抗体和细胞免疫应答。初次免疫后28 d，MF59佐剂组诱导了较高的抗SARS-CoV-2结合抗体和中和抗体，几何平均滴度（geometric mean titer，GMT）分别为89 144和5 418；MF59佐剂组也诱导了较高的针对四价流感病毒（H1N1、H3N2、BV、BY）的血凝抑制抗体，GMT分别为4 457、5 120、1 470和5 881；MF59和AS03佐剂组诱导了较强的针对SARS-CoV-2的Th1型（IFN-γ、IL-2）细胞免疫应答，与正常对照组的斑点形成单位差异均有统计学意义（IFN-γ： H=16.69，P＜0.01； IL-2： H=15.21， P＜0.05）；AS03佐剂组诱导了较强的针对H1N1、H3N2、BV、BY流感病毒的Th1型（IFN-γ、IL-2）细胞免疫应答，与正常对照组的斑点形成单位差异均有统计学意义（IFN-γ： H=12.93、12.17、11.82、13.61，P＜0.05； IL-2： H=12.24、12.42、11.72、12.43， P＜0.05）。结论　不同佐剂配方的SARS-CoV-2和流感病毒联合疫苗的免疫原性及抗原特异性抗体和细胞免疫应答均不同，证明了联合疫苗配方研究中佐剂的重要性。

Objective　To evaluate the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus combined vaccine formulated with 4 adjuvants Al(OH)₃, MF59, AS03 and QS21 in mice.Methods　Adjuvants Al(OH)₃, MF59, AS03 and QS21 were used respectively to prepare SARS-CoV-2 (inactivated) and tetravalent influenza virus (split) combined vaccine. BALB/c mice were immunized by intraperitoneal injection on day 0 (D0) and D14, respectively. Blood samples were collected on D14 and D28 to detect antibody titers against SARS-CoV-2 and hemagglutination inhibition titers of influenza. Spleen lymphocytes were isolated on D28 to detect cellular immune responses to both SARS-CoV-2 and influenza virus.Results　SARS-CoV-2 and influenza virus combined vaccine with different adjuvants induced both antigen-specific antibody responses and cellular immune responses in mice. At D28 post-initial immunization, MF59 adjuvant group induced high levels of SARS-CoV-2 binding antibodies and neutralizing antibodies, with geometric mean titers (GMTs) of 89 144 and 5 418, respectively, and MF59 group also induced high levels of hemagglutination-inhibiting antibodies against the quadrivalent influenza virus strains (H1N1, H3N2, BV, BY), with GMTs of 4 457, 5 120, 1 470 and 5 881, respectively. Both the MF59 and AS03 groups induced robust Th1-type (IFN-γ, IL-2) cellular immune responses against SARS-CoV-2, with spot forming units (SFUs) statistically significantly higher than those of Mock group （IFN-γ： H=16.69，P＜0.01； IL-2： H=15.21， P＜0.05）. The AS03 group induced a strong Th1-type (IFN-γ, IL-2) cellular immune response against the quadrivalent influenza virus strains (H1N1, H3N2, BV, BY), with SFUs statistically significantly higher than those of Mock group （IFN-γ： H=12.93, 12.17, 11.82, 13.61, P＜0.05； IL-2： H=12.24, 12.42, 11.72, 12.43， P＜0.05）.Conclusion　The immunogenicity as well as specific antibody and cellular immune responses of SARS-CoV-2 and influenza virus combined vaccine with different adjuvant formulations are different, indicating the importance of adjuvants in the development of combined vaccine formulations.