Huang Pengwei, Xia Ming, Vago Frank S, Jiang Wen, Tan Ming
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Vaccines (Basel). 2024 Jul 26;12(8):846. doi: 10.3390/vaccines12080846.
The recent worldwide incidence of mpox infection and concerns about future emerging variants of mpox viruses highlight the need for the development of a new generation of mpox vaccines. To achieve this goal, we utilized our norovirus S nanoparticle vaccine platform to produce and evaluate two pseudovirus nanoparticles (PVNPs), S-L1 and S-J1. These PVNPs displayed the L1 neutralizing antigen target of the vaccinia virus and a yet-untested J1 antigen of the mpox virus, respectively, with the aim of creating an effective nanoparticle-based mpox vaccine. Each self-assembled PVNP consists of an inner shell resembling the interior layer of the norovirus capsid and multiple L1 or J1 antigens on the surface. The PVNPs improved the antibody responses toward the displayed L1 or J1 antigens in mice, resulting in significantly greater L1/J1-specific IgG and IgA titers than those elicited by the corresponding free L1 or J1 antigens. After immunization with the S-L1 PVNPs, the mouse sera exhibited high neutralizing antibody titers against the vaccinia virus, and the S-L1 PVNPs provided mice with 100% protection against mortality caused by vaccinia virus challenge. In contrast, the S-J1 PVNPs induced low neutralizing antibody titers and conferred mice weak protective immunity. These data confirm that the L1 protein is an excellent vaccine target and that the readily available S-L1 PVNPs are a promising mpox vaccine candidate worthy of further development.
近期，猴痘感染在全球范围内的发病率以及对未来猴痘病毒新变种的担忧凸显了开发新一代猴痘疫苗的必要性。为实现这一目标，我们利用诺如病毒S纳米颗粒疫苗平台生产并评估了两种假病毒纳米颗粒（PVNP），即S-L1和S-J1。这些PVNP分别展示了痘苗病毒的L1中和抗原靶点和一种尚未测试的猴痘病毒J1抗原，旨在创建一种基于纳米颗粒的有效猴痘疫苗。每个自组装的PVNP都由一个类似于诺如病毒衣壳内层的内壳和表面的多个L1或J1抗原组成。PVNP提高了小鼠对所展示的L1或J1抗原的抗体反应，导致L1/J1特异性IgG和IgA滴度显著高于相应游离L1或J1抗原所引发的滴度。用S-L1 PVNP免疫后，小鼠血清对痘苗病毒表现出高中和抗体滴度，并且S-L1 PVNP为小鼠提供了100%的保护，使其免受痘苗病毒攻击导致的死亡。相比之下，S-J1 PVNP诱导的中和抗体滴度较低，赋予小鼠的保护性免疫较弱。这些数据证实L1蛋白是一个优秀的疫苗靶点，并且现成的S-L1 PVNP是一种有前景的猴痘疫苗候选物，值得进一步开发。
