Scholarlink

Background <p>Rabies remains a devastating and fatal infectious disease worldwide. To date, vaccination is the most reliable and effective strategy for controlling rabies. However, despite the effectiveness of inactivated vaccines, cumbersome vaccination procedures and the high costs of post-exposure prophylaxis impose a significant economic burden, particularly in developing countries with limited access to vaccines. Therefore, there is an urgent need to develop a novel rabies vaccine that reduces costs while enhancing safety and efficacy.</p> Methods <p>We developed a novel mRNA rabies vaccine called RABV-G-LT, which incorporates two immunogens: RABV-G, a glycoprotein designed mainly to elicit neutralizing antibody responses, and RABV-LT, a T-cell immunogen derived from the large protein of the rabies virus. Additionally, we evaluated the immunogenicity of RABV-G-LT in both mice and non-human primates.</p> Results <p>The RABV-LT mRNA vaccination alone induced potent RABV-LT-specific T-cell responses and provided modest protection against rabies virus challenge in mice. Importantly, the dual-immunogen mRNA vaccine RABV-G-LT elicited vigorous and persistent neutralization antibody and T-cell responses, resulting in significantly more efficient clearance of the rabies virus in the brain and spinal cord. This conferred enhanced protection, evidenced by lesser initial weight loss and earlier recovery of body weight compared with the RABV-G mRNA or inactivated vaccine groups. Moreover, RABV-G-LT also mounted persistent strong antigen-specific T-cell and antibody immune responses in nonhuman primates.</p> Conclusions <p>Our study suggested that combining the T-cell immunogen and virus-neutralizing antibody immunogen was a practical approach to strengthening the defense against the rabies virus.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Rabies virus large protein-derived T-cell immunogen facilitates rapid viral clearance and enhances protection against lethal challenge in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月18日

查看全文
  • Shimeng Bai,
  • Xinghao Pan,
  • Tianhan Yang,
  • Nan Gao,
  • Cuisong Zhu,
  • Ai Xia,
  • Meiqi Feng,
  • Miaomiao Zhang,
  • Xiaoyan Zhang,
  • Jianqing Xu

摘要

Background

Rabies remains a devastating and fatal infectious disease worldwide. To date, vaccination is the most reliable and effective strategy for controlling rabies. However, despite the effectiveness of inactivated vaccines, cumbersome vaccination procedures and the high costs of post-exposure prophylaxis impose a significant economic burden, particularly in developing countries with limited access to vaccines. Therefore, there is an urgent need to develop a novel rabies vaccine that reduces costs while enhancing safety and efficacy.

Methods

We developed a novel mRNA rabies vaccine called RABV-G-LT, which incorporates two immunogens: RABV-G, a glycoprotein designed mainly to elicit neutralizing antibody responses, and RABV-LT, a T-cell immunogen derived from the large protein of the rabies virus. Additionally, we evaluated the immunogenicity of RABV-G-LT in both mice and non-human primates.

Results

The RABV-LT mRNA vaccination alone induced potent RABV-LT-specific T-cell responses and provided modest protection against rabies virus challenge in mice. Importantly, the dual-immunogen mRNA vaccine RABV-G-LT elicited vigorous and persistent neutralization antibody and T-cell responses, resulting in significantly more efficient clearance of the rabies virus in the brain and spinal cord. This conferred enhanced protection, evidenced by lesser initial weight loss and earlier recovery of body weight compared with the RABV-G mRNA or inactivated vaccine groups. Moreover, RABV-G-LT also mounted persistent strong antigen-specific T-cell and antibody immune responses in nonhuman primates.

Conclusions

Our study suggested that combining the T-cell immunogen and virus-neutralizing antibody immunogen was a practical approach to strengthening the defense against the rabies virus.