Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates

Affiliations

• Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA
• Moderna Inc., Cambridge, MA, USA
• Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
• National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA, USA
• Department of Virology, Immunology, and Microbiology, Boston University School of Medicine, Boston, MA, USA
• Department of Biology, Boston University, Boston, MA, USA

PMID: None DOI: None

Summary

In 2022, mpox virus (MPXV) spread worldwide, causing 99,581 mpox cases in 121 countries. Modified vaccinia Ankara (MVA) vaccine use reduced disease in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central Africa of clade I virus. These outbreaks highlight the threat of zoonotic spillover by Orthopoxviruses. mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine expressing MPXV surface proteins, was tested in a lethal MPXV primate model. Similar to MVA, mRNA-1769 conferred protection against challenge and further mitigated symptoms and disease duration. Antibody profiling revealed a collaborative role between neutralizing and Fc-functional extracellular virion (EV)-specific antibodies in viral restriction and ospinophagocytic and cytotoxic antibody functions in protection against lesions. mRNA-1769 enhanced viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.

在2022年，猴痘病毒（mpox, MPXV）在全球范围内传播，导致121个国家报告了99,581例mpox病例。改良的安卡拉痘苗（MVA）疫苗的使用在高风险人群中减少了疾病，但未能提供完全的保护。MVA的生产和分发滞后导致了MPXV的进一步传播，2023年报告了12,000例病例，并且在中非发生了I型病毒的额外暴发。这些疫情突显了正痘病毒（Orthopoxviruses） zoonotic spillover的威胁。mRNA-1769是一种mRNA-脂质纳米颗粒（LNP）疫苗，能够表达MPXV表面蛋白，并在致死性MPXV非人灵长类动物模型中进行了测试。与MVA类似，mRNA-1769对挑战提供了保护，并进一步缓解了症状和疾病持续时间。抗体分析显示，中和抗体与Fc功能的细胞外病毒（EV）特异性抗体在病毒限制中的协同作用，以及嗜酸性吞噬和细胞毒性抗体功能在对抗损伤中的保护作用。与MVA相比，mRNA-1769增强了病毒控制和疾病缓解，突显了mRNA疫苗在缓解未来大流行威胁中的潜力。

References 

• Koplan, J.P. Foster, S.O. Smallpox: clinical types, causes of death, and treatment J. Infect. Dis. 1979; 140:440-441
• Breman, J.G. Kalisa-Ruti, R. Steniowski, M.V. Human monkeypox, 1970–79 Bull. World Health Organ. 1980; 58:165-182
• Rimoin, A.W. Mulembakani, P.M. Johnston, S.C. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo Proc. Natl. Acad. Sci. USA. 2010; 107:16262-16267
• Deputy, N.P. Deckert, J. Chard, A.N. Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States N. Engl. J. Med. 2023; 388:2434-2443