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 naive 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.