Characterization of immune response against monkeypox virus in cohorts of infected patients, historic and newly vaccinated subjects

Monkeypox virus (MPXV) is a zoonotic disease endemic in the rainforest countries of Central and West Africa. Understanding the immune response in zoonosis is fundamental to prevent and contrast viral spreading. MPXV is a close relative of Variola (smallpox) virus and vaccination with vaccinia virus gives approximatively 85% of protection against MPXV. With the emergence of the recent MPXV outbreak, JYNNEOS vaccine has been proposed to individuals at high‐risk of exposure. Comparative data on MPXV immune response in vaccinated or infected subjects are still limited. Here we set‐up an immunofluorescence method for the evaluation of humoral response elicited by natural infection and healthy vaccinated subjects, including historically smallpox‐vaccinated individuals and newly vaccinated subjects. Neutralization assay was also included, and in vaccinated subjects, cell‐mediated response was evaluated. We observed that the natural infection produces a strong immune response that can control the disease. In naïve subjects, a second dose boosts the serological response to levels similar to those of the MPXV patients. Last, smallpox‐vaccinated controls retain a degree of protection, even after years from vaccination, most visible in the t‐cellular response.