PDF(Pubmed)
Abstract：
The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo raised public health concerns about the threat of human-to-human transmission of zoonotic diseases. Currently available vaccines may not be sufficient to contain outbreaks of a more transmissible and pathogenic orthopoxvirus. Development of a safe, effective, and scalable vaccine against orthopoxviruses to stockpile for future emergencies is imminent. In this study, we have developed an mRNA vaccine candidate, ALAB-LNP, expressing four vaccinia viral antigens A27, L1, A33, and B5 in tandem in one molecule, and evaluated the vaccine immunogenicity in rodent models. Immunization of animals with the candidate mRNA vaccine induced a potent cellular immune response and long-lasting antigen-specific binding antibody and neutralizing antibody responses against vaccinia virus. Strikingly, the sera from the vaccine-immunized mice cross-reacted with all four homologous antigens of multiple orthopoxviruses and neutralized monkeypox virus in vitro, holding promise for this mRNA vaccine candidate to be used for protection of humans from the infection of monkeypox and other orthopoxvirus.
摘要：
2022年全球爆发的猴痘病毒感染人类和2023年在刚果民主共和国发生的更具毒性的猴痘病毒的记录，引起了公众对人与人之间传播人畜共患疾病威胁的关注。目前可用的疫苗可能不足以遏制更具传染性和致病性的正痘病毒的爆发。安全的发展，有效,针对正痘病毒的可扩展疫苗，以储备未来的紧急情况迫在眉睫。在这项研究中,我们开发了一种mRNA候选疫苗，ALAB-LNP,在一个分子中串联表达四种牛痘病毒抗原A27，L1，A33和B5，并在啮齿动物模型中评估疫苗的免疫原性。用候选mRNA疫苗对动物的免疫诱导针对牛痘病毒的有效细胞免疫应答和持久的抗原特异性结合抗体和中和抗体应答。引人注目的是，疫苗免疫小鼠的血清在体外与多种正痘病毒和中和猴痘病毒的所有四种同源抗原交叉反应，该mRNA候选疫苗有望用于保护人类免受猴痘和其他正痘病毒的感染。
