Safety and Efficacy of Repurposed Smallpox Vaccines Against Mpox: A Critical Review of ACAM2000, JYNNEOS, and LC16

Since 2022, outbreaks of monkeypox (Mpox), which is caused by the monkeypox virus (MPXV), have been documented in more than 116 nations, making it a serious danger to world health. Despite being self-limiting in most cases, Mpox can lead to severe illness and even death, especially among high-risk populations like the LGBTQI + community. Hence, there is an urgent need for effective prevention and treatment strategies, with vaccination playing a crucial role. This paper explores the safety and efficacy of three key vaccines; ACAM2000, JYNNEOS, and LC16 that are repurposed from smallpox vaccines to combat Mpox. ACAM2000, a replication-competent vaccinia virus vaccine, has shown high effectiveness but is associated with serious adverse reactions, including myocarditis and progressive vaccinia. JYNNEOS, a modified vaccinia Ankara vaccine, offers a more favorable safety profile with fewer severe side effects, demonstrating 82% vaccine effectiveness in preventing Mpox. LC16, another smallpox vaccine, shows strong protective efficacy in animal models and excellent safety outcomes in human trials. Our assessment of the available primary data suggests that amongst the three candidates, JYNNEOS emerges as the most promising candidate for widespread use due to its strong effectiveness and superior safety profile. However, while Mpox vaccines provide robust protection, their varying safety profiles highlight the need for tailored vaccination strategies based on individual health factors. The authors therefore emphasize balancing vaccine efficacy with safety risks, particularly in vulnerable populations. Further research and surveillance are essential to optimize vaccination strategies and control Mpox outbreaks worldwide.