Lulu Zuo, Qixing Liu, Ke Zhang, Lu Zhao, Siyu Lin, You Dai, Yun Sun, Yingwen Li, Pingping Zhang, Huyan Shen, Dongmei He, Shuang Ma, Xianhua Long, Yanhua Chen, Yusi Luo, Gary Wong
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引用次数: 0
Abstract
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.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.