During an outbreak of monkeypox in the UK in 2018, a third generation smallpox vaccine, Imvanex, was used for the first time to immunise healthcare workers who had been, or were expected to be, in contact with cases of monkeypox. This study will examine the antibody responses in these healthcare workers compared to control groups, to provide evidence that the vaccine can produce a response consistent with protection when used in this context.

This study intends to describe antibody responses to a third generation smallpox vaccine, Imvanex® (MVA-BN, Bavarian Nordic GmBH; also known as Imvamune®), in cohorts of individuals who received the vaccine for pre-exposure or post-exposure prophylaxis against monkeypox during a monkeypox outbreak in the UK. In addition to quantifying anti-vaccinia virus antibody responses to vaccine, the study intends to demonstrate that vaccine-induced antibodies neutralise the specific monkeypox viruses involved in the UK outbreak, and also reference monkeypox viruses. The use of Imvanex® during the UK outbreak represents the first ever use of Imvanex® as a public health intervention for a monkeypox outbreak, and this study will provide an opportunity to quantify and characterise antibody responses to Imvanex® administered in a non-trial setting.

Inclusion criteria for pre-exposure prophylaxis cases:

• A High Consequence Infectious Disease (HCID) Centre healthcare worker involved in the care of a confirmed monkeypox case
• AND the individual has received Imvanex® during the outbreak period
• AND no known unprotected exposure to a monkeypox case (i.e. pre-exposure indication for vaccination)

Inclusion criteria for post-exposure prophylaxis cases:

• A healthcare worker
• AND the individual has received Imvanex® during the outbreak period
• AND unprotected exposure to a monkeypox case is believed to have occurred (i.e. post-exposure indication for vaccination)

Inclusion criteria for control group 1 (unvaccinated HCID staff caring for confirmed cases):

• A High Consequence Infectious Disease (HCID) Unit healthcare worker involved in the care of a confirmed monkeypox case
• AND the individual has NOT received Imvanex® during the outbreak period
• AND no known unprotected exposure to a monkeypox case

Inclusion criteria for control group 2 (general healthcare workers):

• A healthcare worker NOT involved in the care of a confirmed monkeypox case
• AND the individual has NOT received Imvanex® during the outbreak period
• AND no known unprotected exposure to a monkeypox case

Exclusion criteria for all participants:

• Refusal by participant
• Age less than 18 years

Healthcare workers at NHS Airborne HCID Centres, and healthcare workers at other NHS hospitals that cared for monkeypox cases before they were transferred to HCID Centres.