Independent report

JCVI statement on mpox vaccination as a routine programme

Published 10 November 2023

Background

The Joint Committee on Vaccination and Immunisation (JCVI) is an expert scientific advisory committee which advises the UK government on vaccination and immunisation matters.

Mpox (previously referred to as monkeypox) is a rare disease caused by infection with the mpox virus. Mpox is an orthopox virus and therefore related to the viruses which cause smallpox and cowpox.

Before spring 2022, UK mpox cases were either associated with travel to or from countries where mpox is endemic (mostly countries in West or Central Africa) or had documented epidemiological links to these cases. Transmission of mpox may occur when an individual comes into close contact with an animal or human currently infected with the mpox virus. Indirect transmission may also occur from close contact with material or surfaces contaminated with the virus.

In May 2022, sustained transmission of mpox virus was identified in the UK leading to a large outbreak different to the pattern and scale that had previously been observed. Cases were primarily identified among gay, bisexual and other men who have sex with men (GBMSM) without a history of travel to endemic countries, therefore suggesting community transmission. Epidemiological surveillance suggested that transmission was occurring from direct person-to-person contact in defined sexual networks of GBMSM. Cases were identified in every geographical region of the UK although most cases were in London residents.

The UK Health Security Agency (UKHSA) requested endorsement from the JCVI on the optimal vaccination strategy to support the outbreak response. This advice was developed based on the observed epidemiology and projected vaccine supply at that time. 

At the time of the advice, there was no vaccine licensed for protection against mpox. However there was good evidence that the Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN) smallpox vaccine would provide cross-protection to mpox when given pre-exposure. In September 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) approved MVA-BN for immunisation against mpox.

As an outbreak response, a limited offer of pre-exposure vaccination was recommended in GBMSM who may be at highest risk of exposure to mpox and as occupational vaccination to workers at high risk of exposure. Due to the limited global supply of vaccines, it was initially recommended that first doses should be prioritised.

Due to very limited evidence on effectiveness when giving the vaccine post-exposure, vaccination was recommended for close contacts ideally within 4 days of exposure, increasing up to 14 days in those who were at higher risk of complications from mpox.

In August 2022, the Food and Drug Administration (FDA) in the United States issued an Emergency Use Authorization (EUA) to use the vaccine for active immunisation by intradermal injection as it has been shown to be immunologically non-inferior. For intradermal administration 0.1 millilitres of vaccine is used compared with the standard 0.5ml dose when given by sub-cutaneous injection. This approach was also endorsed by the European Medicines Agency. The JCVI endorsed this approach to maximise the number of doses that can be administered without compromising immunity.

In September 2022, the JCVI was asked to consider how remaining doses should be allocated - to prioritise second doses in the highest risk group, or to expand the eligible groups for first dose to those at intermediate risk. The committee reviewed modelling estimates on the impact of prioritising second doses in the highest risk group, compared with prioritising expansion of vaccination with a single dose to a wider group. The JCVI endorsed the approach to offer 2 doses to those in the existing target groups for pre-exposure vaccination.

The purpose of this JCVI statement is to advise on the approach to mpox vaccination after the 2022 to 2023 outbreak response.

2022 mpox outbreak

Since May 2022, a total of 3,820 cases of mpox have been detected in the UK. The overwhelming majority of these cases were reported in 2022 (UKHSA).

Following on from the start of the outbreak in May 2022, the number of cases increased sharply through June, peaking in mid-July. The vast majority of these cases were in GBMSM, most of whom reported markers of being in dense interconnected sexual networks such as multiple recent sexual partners or a recent bacterial sexually transmitted infection (STI) diagnosis. The number of cases started to tail off from the peak in summer 2022, and by the end of the year very few cases were being reported.

Between 1 January and 31 October 2023, a total of 88 cases have been detected in the UK with at least 41% of these cases reported to have been acquired outside the UK. Although some mpox cases have been reported to be in vaccinated individuals (having received at least one dose of vaccine), none of the individuals who were hospitalised with mpox in 2023 had been vaccinated. High vaccine coverage in eligible GBMSM was achieved by the end of 2022 but it’s expected that some breakthrough infections would be seen as protection from the vaccine against symptomatic mpox has been estimated at 78% from a single dose (Bertran and others) and by definition, those who had been vaccinated were at high risk. Most cases continue to be located in London.

Targeted pre-exposure vaccination commenced in June 2022 following advice from the JCVI and, to date, over 78,000 first doses and over 43,000 second doses have been given. Data from a community survey indicated that uptake of at least one dose of mpox vaccination was 69% among those eligible (Ogaz and others). This reactive vaccination offer ended nationally in summer 2023, although vaccination has continued to be offered in London and Manchester where clusters of locally transmitted cases have been seen.

Evidence

In June and September 2023, the JCVI met to discuss the potential for an ongoing mpox programme.

Modelling of the impact and cost-effectiveness of an mpox vaccination programme was undertaken by UKHSA and the University of Bristol. This model looked at the impact and cost-effectiveness of vaccinating GBMSM at high risk of exposure to mpox.

This transmission dynamic model included data from the 2022 outbreak on disease severity, vaccine effectiveness and sexual behavioural modification (Zhang and others). Despite there being importation of mpox cases during 2023, no resulting sustained outbreak was seen. Therefore the model was calibrated accordingly, including with an estimated duration of protection from vaccination which would fit the observed data.

The cost-effectiveness model looked at both the costs of treatment of mpox and costs associated with vaccination, it also accounted for the public health response costs. During the outbreak in 2022, significant public health response costs were incurred due to activities including surveillance and contact tracing.

The model analysed vaccination strategies including reactive scenarios (initiating a vaccination programme in response to an outbreak) and pre-emptive scenarios (offering vaccination as a routine programme) with high and low rates of vaccination. The results from the modelling indicated that any vaccination strategy reduces outbreak size and duration. While a pre-emptive programme could prevent outbreaks altogether, a reactive programme could still reduce infections to a low level.

Over a 20-year time horizon, all vaccination scenarios were shown to be cost-saving compared with no vaccination. However the costs of different scenarios differed. Total costs are always higher when a higher rate of vaccination is assumed due to the increase in the number of doses administered.

When including the public health response costs, almost all scenarios were shown to be cost-saving. However the pre-emptive programme (with low rate of vaccination) dominated. There was little additional benefit from vaccination at a higher rate.

When the public health response costs were not taken into account, the reactive vaccination programme scenario (with a low rate of vaccination) dominated the cost-effectiveness. Pre-emptive vaccination without accounting for public health response costs was not estimated to be cost-saving except at a low vaccination rate based on the parameters assumed; however is likely to still be cost-effective.  

There were still a number of uncertainties about the data used in the modelling analysis, including the true duration of protection given by vaccination, true vaccine effectiveness and immunity following natural infection. All analysis had been carried out assuming a full dose of vaccine would be used rather than including intradermal dose sparing. The JCVI considered that additional data should be reviewed once available.

JCVI advice

The JCVI advises that an ongoing routine vaccination strategy for protection against mpox should be developed to prevent future outbreaks and protect those at risk of exposure.

A pre-emptive vaccine strategy could prevent outbreaks occurring and would also allow vaccines to be offered routinely through sexual health services on an ongoing basis, as opposed to an outbreak response which had caused a significant disruption in sexual health services, impacting on their ability to continue with routine work. The public health response costs which were associated with the outbreak were also saved, making a pre-emptive vaccination strategy the preferred approach.

The JCVI advises that pre-exposure vaccination should target GBMSM who are at highest risk of exposure to mpox, to be identified via sexual health services using markers of high-risk behaviour similar to those used to assess eligibility for HIV pre-exposure prophylaxis (PrEP) but applied regardless of HIV status. These risk criteria would include:

• a recent history of multiple partners
• participating in group sex
• attending sex-on-premises venues
• a proxy marker such as a bacterial STI within the last year

Efforts should be made to ensure that vaccine is offered equitably to those at equivalent risk including transgender women or gender-diverse people assigned male at birth.

Guidelines for occupational pre-exposure vaccination in healthcare and laboratory workers can be found in chapter 29 of the Green Book.

The JCVI keeps all of its advice under review and therefore once further information relating to the duration of protection against mpox from both vaccination and natural infection become available, the modelling work and resulting advice will be reviewed.

References

Bertran M, Andrews N, Davison C and others. Effectiveness of one dose of MVA-BN smallpox vaccine against mpox in England using the case-coverage method: an observational study. Lancet Infectious Diseases 2023; volume 23, issue 7, pages 828-835.

Ogaz D, Enayat Q, Brown JRG and others. Mpox diagnosis history, behavioural risk modification and vaccination uptake in gay, bisexual and other men who have sex with men in the UK: findings from a large online community cross-sectional survey (RiiSH-Mpox) undertaken November and December 2022. MedRxiv 2023.

UKHSA research and analysis. Mpox (monkeypox) outbreak epidemiological overview, 3 November 2023.

Zhang XS, Mandal S, Mohammed H and others. Transmission dynamics and effect of control measures on the 2022 outbreak of mpox among gay, bisexual and other men who have sex with men in England: a mathematical modelling study. Lancet Infectious Diseases 2023, online publication ahead of print.