Cham Lamin B, Hamdan Thamer A, Bhat Hilal, Sirajo Bello, Ali Murtaza, Tabbara Khaled Saeed, Farid Eman, Barbouche Mohamed-Ridha, Adomati Tom
Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Health Sciences, Arabian Gulf University, Manama 26671, Bahrain.
Department of Clinical Medicine, Aarhus University, 8220 Aarhus, Denmark.
Vaccines (Basel). 2025 May 31;13(6):602. doi: 10.3390/vaccines13060602.
BACKGROUND/OBJECTIVES: CD47 is a cell surface glycoprotein moderately expressed in healthy cells and upregulated in cancer and viral infected cells. CD47's interaction with signal regulatory protein alpha (SIRPα) inhibits phagocytic cells and its interaction with thrombospondin-1 inhibits T cell response. Experimental evidence has revealed that the blockade of CD47 resulted in the increased activation and function of both innate and adaptive immune cells, therefore exerting antitumoral and antiviral effects. Recent studies have shown that the combination of vaccines and immune checkpoint inhibitors could be a promising approach to increasing vaccine immunogenicity. Here, we investigated the vaccinal effect of anti-CD47 antibodies and discussed the possibilities of combining anti-CD47 treatments with vaccines. METHODS: Using vesicular stomatitis virus (VSV), a widely used replication-competent vaccine vector, we evaluated the impact of the immunotherapeutic blockade of CD47 on cellular, humoral, and protective immunity. We infected C57BL/6 mice with VSV, treated them with anti-CD47 antibodies or an isotype, and evaluated the total immunoglobulin (Ig), IgG neutralizing antibodies, B cell activation, CD8+ T cell effector function, and survival of the mice. RESULTS: We found that the treatments of anti-CD47 antibodies led to significantly increased Ig and IgG neutralizing antibody levels compared to the isotype treatment. Flow cytometric analysis of B cells revealed no difference in the number of circulating B cells; however, we observed an increased surface expression of CD80 and CD86 in B cells among anti-CD47-treated mice. Further analysis of the impact of CD47 blockade on T immunity revealed a significantly higher percentage of IFN-γ CD4 and IFN-γ CD8 T cells in anti-CD47-treated mice. Upon infecting mice with a lethal VSV dose, we observed a significantly higher survival rate among the anti-CD47-treated mice compared to control mice. CONCLUSIONS: Our results indicate that anti-CD47 treatment induces a stronger cellular and humoral immune response, leading to better protection. As such, immunotherapy by CD47 blockade in combination with vaccines could be a promising approach to improve vaccine efficacy.
背景/目的：CD47是一种细胞表面糖蛋白，在健康细胞中适度表达，在癌症和病毒感染细胞中上调。CD47与信号调节蛋白α（SIRPα）的相互作用会抑制吞噬细胞，其与血小板反应蛋白-1的相互作用会抑制T细胞反应。实验证据表明，阻断CD47会导致先天性和适应性免疫细胞的激活和功能增强，从而发挥抗肿瘤和抗病毒作用。最近的研究表明，疫苗与免疫检查点抑制剂联合使用可能是提高疫苗免疫原性的一种有前景的方法。在此，我们研究了抗CD47抗体的疫苗效应，并探讨了将抗CD47治疗与疫苗联合使用的可能性。 方法：使用水泡性口炎病毒（VSV），一种广泛使用的具有复制能力的疫苗载体，我们评估了CD47免疫治疗性阻断对细胞免疫、体液免疫和保护性免疫的影响。我们用VSV感染C57BL/6小鼠，用抗CD47抗体或同型对照进行治疗，并评估总免疫球蛋白（Ig）、IgG中和抗体、B细胞激活、CD8 + T细胞效应功能以及小鼠的存活率。 结果：我们发现，与同型对照治疗相比，抗CD47抗体治疗导致Ig和IgG中和抗体水平显著升高。对B细胞的流式细胞术分析显示循环B细胞数量没有差异；然而，我们观察到抗CD47治疗的小鼠中B细胞表面CD80和CD86的表达增加。对CD47阻断对T免疫影响的进一步分析显示，抗CD47治疗的小鼠中IFN-γ CD4和IFN-γ CD8 T细胞的百分比显著更高。在用致死剂量的VSV感染小鼠后，我们观察到抗CD47治疗的小鼠的存活率显著高于对照小鼠。 结论：我们的结果表明，抗CD47治疗可诱导更强的细胞免疫和体液免疫反应，从而提供更好的保护。因此，通过阻断CD47与疫苗联合进行免疫治疗可能是提高疫苗疗效的一种有前景的方法。
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