Immunobiology of HIV, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Clinical Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Front Immunol. 2021 Nov 2;12:771359. doi: 10.3389/fimmu.2021.771359. eCollection 2021.
Recent studies showed that immunological tolerance may restrict the development of Env-specific autoreactive broadly neutralizing antibodies. This evidence is consistent with the finding that Env immunization of a systemic lupus erythematosus (SLE) murine model produced antibodies that neutralize tier 2 HIV-1 strains. In this study, we address the possibility of eliciting neutralizing anti-Env antibodies in other autoimmune diseases such as multiple sclerosis (MS). While, as reported for SLE, we showed for the first time that a small number of HIV-1 negative, relapsing remitting MS patients exhibited antibodies with neutralizing properties, our attempts at inducing those antibodies in a EAE mouse model of MS failed. The success in eliciting Env-specific neutralizing antibodies might be related to the specific characteristics of the autoimmune disease, or it might rely in improving the vaccination design. Studies using mouse models are useful to gain insight in how HIV-specific neutralizing antibody responses are regulated in order to develop a protective HIV-1 vaccine.
最近的研究表明,免疫耐受可能会限制 Env 特异性自身反应性广谱中和抗体的产生。这一证据与系统性红斑狼疮 (SLE) 小鼠模型的 Env 免疫产生能够中和 HIV-1 2 型毒株的抗体的发现一致。在这项研究中,我们探讨了在其他自身免疫性疾病(如多发性硬化症 (MS))中引发中和抗 Env 抗体的可能性。虽然我们如报告 SLE 中那样,首次表明少数 HIV-1 阴性、复发缓解型 MS 患者表现出具有中和特性的抗体,但我们在 MS 的 EAE 小鼠模型中诱导这些抗体的尝试失败了。成功引发 Env 特异性中和抗体可能与自身免疫性疾病的特定特征有关,也可能依赖于改进疫苗设计。使用小鼠模型的研究有助于深入了解 HIV 特异性中和抗体反应是如何受到调节的,以便开发出保护性的 HIV-1 疫苗。