Cohort Study of Healthcare Workers Receiving Imvanex®

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Cohort Study of Serological Responses to MVA-BN Smallpox Vaccine (Imvamex®) Administered During a Monkeypox Outbreak in the UK

Conditions
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Monkeypox

Intervention / Treatment
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* Other: Blood draw


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pre-exposure prophylaxis recipients<br>40 healthcare workers who provide specialist medical care to patients with monkeypox and who received vaccine as pre-exposure prophylaxis. | Other: Blood draw<br>* Blood draw to obtain serum to determine anti-orthopox antibody titres.<br>|
| Post-exposure prophylaxis recipients<br>40 healthcare workers who received vaccine as post-exposure prophylaxis following monkeypox-exposure risk assessments. | Other: Blood draw<br>* Blood draw to obtain serum to determine anti-orthopox antibody titres.<br>|
| Control Group 1<br>20 healthcare workers who provided specialist medical care to patients with monkeypox but declined the offer of vaccine as pre-exposure prophylaxis. | Other: Blood draw<br>* Blood draw to obtain serum to determine anti-orthopox antibody titres.<br>|
| Control Group 2<br>Healthcare workers not involved in the care of, and have not had known exposure to, patients with monkeypox and, therefore, were not offered vaccine. | Other: Blood draw<br>* Blood draw to obtain serum to determine anti-orthopox antibody titres.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody responses to first dose of Imvanex® | The proportion of participants with anti-orthopox antibodies when measured at a single time point between days 28 and 56 following first dose of Imvanex®. | 28-56 days following immunisation | 
| Antibody titres following first dose of Imvanex® | Geometric mean titres (GMTs) of anti-orthopox antibodies when measured at a single time point between days 28 and 56 following first dose of Imvanex®. | 28-56 days following immunisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody responses to second dose of Imvanex® | The proportion of participants who have anti-orthopox antibodies when measured at day 14 following the second dose of Imvanex®, if a subset of individuals receive a second dose of Imvanex® during the lifetime of the study. | 28-56 days following immunisation | 
| Antibody titres following second dose of Imvanex® | The geometric mean titres (GMTs) of anti-orthopox antibodies when measured at day 14 following the second dose of Imvanex®, if a subset of individuals receive a second dose of Imvanex®. | 28-56 days following immunisation | 
| Neutralising antibody responses to first dose of Imvanex® | The proportion of participants who have demonstrable neutralising antibodies against the specific monkeypox viruses involved in the UK outbreak, in addition to reference monkeypox viruses. | 28-56 days following immunisation | 
| Adverse events reported following vaccination with Imvanex® | Adverse events and serious adverse events by reported frequencies (reported retrospectively). | 28-56 days following immunisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunisation, Modified Vaccinia Ankara, Imvanex, Imvamune, Vaccine