Respiratory Syncytial Virus (RSV) represents a significant threat, being a primary cause of critical lower respiratory tract infections and fatalities among infants and the elderly worldwide, and poses a challenge to global public health. This urgent public health challenge necessitates the swift development of safe and effective vaccines capable of eliciting robust immune responses at low doses. Addressing this need, our study investigated five self-amplifying RNA (sa-mRNA) candidate vaccines that encode the various pre-fusion conformations of the RSV fusion protein. When administered via low-dose intramuscular injection to 8-month-old elderly mice, these vaccines triggered potent humoral reactions and Th1-biased cellular immunity. A prime-boost strategy followed by challenge with a lethal, mouse-adapted RSV strain showed that three of these sa-mRNA candidates achieved over 80% survival rates. An immune correlates of protection (CoP) analysis contrasting immunized survivors with non-survivors suggest that the titers of IgG and neutralizing antibody are associated with vaccine-mediated protection from RSV infection. Our results highlight the utility of sa-mRNA vaccines to play a crucial role in forging an effective defense against RSV, addressing a critical need in protecting vulnerable populations against this virus.

中文翻译：

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自扩增 mRNA 疫苗可保护老年 BALB/c 小鼠免受致命的呼吸道合胞病毒感染。


呼吸道合胞病毒 （RSV） 是一种重大威胁，是全球婴儿和老年人严重下呼吸道感染和死亡的主要原因，并对全球公共卫生构成挑战。这一紧迫的公共卫生挑战需要迅速开发安全有效的疫苗，能够在低剂量下引发强大的免疫反应。为了满足这一需求，我们的研究调查了五种编码 RSV 融合蛋白各种融合前构象的自扩增 RNA （sa-mRNA） 候选疫苗。当通过低剂量肌肉注射给 8 个月大的老年小鼠时，这些疫苗触发了强烈的体液反应和 Th1 偏向细胞免疫。初免-增强策略，然后用致命的小鼠适应的 RSV 毒株进行攻击，结果表明，这些 sa-mRNA 候选者中有 3 个实现了超过 80% 的存活率。免疫保护相关性 （CoP） 分析将免疫幸存者与非幸存者进行对比，表明 IgG 和中和抗体的滴度与疫苗介导的 RSV 感染保护有关。我们的结果强调了 sa-mRNA 疫苗在有效防御 RSV 方面发挥关键作用的效用，解决了保护弱势群体免受这种病毒侵害的关键需求。