Analogous Humoral Antigen Recognition between Smallpox-Vaccinated and Mpox-Infected Individuals

Abstract

In early 2022, a cluster of Monkeypox (Mpox) virus (MPXV) cases were identified within the UK with no prior travel history, suggesting localised transmission of MPXV within the UK. Cases currently exceed 80,000 worldwide, primarily affecting gay, bisexual, and other men who have sex with men. Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals as means to provide protection and limit the spread of Mpox.

We have developed a comprehensive array of ELISA assays to study antibodies induced by Smallpox vaccination and Mpox-infection, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with one, two, or three doses of Smallpox (Vaccinia) vaccination, or with prior infection with MPXV were tested against these antigens. In addition, we developed a pooled antigen ELISA to detect antibody responses induced by Smallpox vaccination or MPXV infection.

Using diverse poxvirus antigen ELISAs, we observe that one dose of Smallpox vaccination induces a low number of antibodies, with a second dose inducing considerably higher antibody responses with waning observed 60 days later. In addition, we were able to monitor temporal changes in antibody binding to a number of different poxvirus antigens after vaccination. Prior MPXV infection, both Clades IIa & IIb, induces variable antibody responses, but similarly to poxvirus antigens observed in Smallpox-vaccinated individuals. Using a pooled-antigen ELISA, we also demonstrate a sensitivity of 97.98% (92.93-99.64) and specificity of 98.21% (96.63-99.06) in detecting poxvirus antibodies post-vaccination/post-MPXV infection.

Here, we show that both MPXV-infected and Smallpox-vaccinated individuals mount antibodies able to bind a diverse but core set of poxvirus antigens, with low levels of antibodies post-dose one, but considerably higher post-dose two. These data together help us to further elucidate the immunology of Smallpox-vaccination and poxvirus infection, aiding in future vaccine development and immunology studies. 

Note: This conference abstract was presented at the 17th Vaccine Conference organized by the journal Vaccine. This abstract has not been screened by SSRN for potential for public harm and should not be used to inform any clinical decision making. No competing interests or funding statements have been declared.