Independent report

JCVI statement on vaccine dose prioritisation in response to the monkeypox outbreak

Published 23 September 2022

Background

In May 2022, sustained transmission of monkeypox virus was identified in the UK. This outbreak differs from previous UK monkeypox outbreaks in which cases were either imported from countries where monkeypox is endemic (mostly countries in West and Central Africa) or had documented epidemiological links to imported cases, without community transmission.

Monkeypox is a rare disease caused by the monkeypox virus which is related to the viruses that cause smallpox and cowpox. Transmission may occur when an individual comes into close contact with an animal or human that has previously had the monkeypox virus. It may also occur indirectly, such as when a person comes into close contact with material contaminated with the virus.

In the current outbreak, cases have been primarily identified among gay, bisexual and other men who have sex with men (GBMSM) without history of travel to endemic countries. Epidemiological data suggests transmission has been occurring through direct person-to-person contact in defined sexual networks of GBMSM since at least April 2022. While most cases are in London residents, there have been cases identified in every region of the UK.

In September 2022, the smallpox vaccine Modified Vaccinia Ankara – Bavarian Nordic (MVA-BN) was approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for immunisation against monkeypox. This vaccine has been used in the UK to support the control of previous monkeypox outbreaks. This vaccine is distributed under the brand names Imvanex (approved by the MHRA in the UK and the European Medicines Agency in Europe for the prevention of smallpox and monkeypox) and JYNNEOS (approved in the United States for the prevention of smallpox and monkeypox).

The UK Health Security Agency (UKHSA) has been working closely with the JCVI on the role of vaccination to prevent further cases and limit ongoing transmission.

Previous advice from the JCVI

In May 2022, the JCVI met to discuss and provide their advice on vaccination against monkeypox in the context of the ongoing outbreak. UKHSA consulted with the JCVI and published their monkeypox guidance vaccination strategy statement in June 2022 based on the advice given. The initial JCVI advice was formed based on the observed epidemiology and projected vaccine supply at the time.

The overall aim of the advised strategy is to interrupt transmission among those at increased risk from monkeypox. The JCVI also strongly endorsed further procurement of doses of MVA-BN where possible.

Pre-exposure vaccination was recommended in GBMSM who may be at highest risk of exposure to monkeypox and as occupational vaccination to workers at high risk of exposure. Those identified to be in eligible groups for pre-exposure vaccination include:

• GBMSM at highest risk of exposure 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 sexually transmitted infection (STI) within the last year
• occupational vaccination:
  • staff expected to provide care to monkeypox cases in high-consequence infectious disease (HCID) units
  • staff in sexual health clinics designated to assess suspected cases
  • staff in additional hospitals outside HCID units designated to care for monkeypox patients
  • workers in specialist laboratories where pox viruses (such as monkeypox or genetically modified vaccinia) are handled, and others who work in specialist and reference laboratories with an identifiable risk of exposure as per Advisory Committee on Dangerous Pathogens (ACDP) guidance
  • staff regularly undertaking environmental decontamination around cases of monkeypox, even if they will be wearing full personal protective equipment

Other healthcare staff should be able to avoid inadvertent exposure by ensuring suspected monkeypox cases are assessed by designated staff, or by wearing appropriate personal protective equipment.

Due to the limited global supply of vaccines, it was recommended that first doses should be prioritised during this outbreak, with the offer of a second dose for those who continue to be at an increased risk of exposure.

Due to the very limited evidence on the effectiveness when given post-exposure, vaccination was recommended to be given to close contacts of cases ideally within 4 days of exposure, up to 14 days in those who are at higher risk of complications of monkeypox.

In August 2022, the Food and Drug Administration (FDA) in the United States issued an Emergency Use Authorisation for the emergency use of JYNNEOS for active immunisation against monkeypox by intradermal injection.

Intradermal administration uses 0.1ml of the vaccine and has been shown to be immunologically non-inferior to the standard 0.5ml dose given by subcutaneous administration. The European Medicines Agency Emergency Task Force released a statement concluding that intradermal use of MVA-BN vaccine was acceptable in view of the outbreak situation and significant vaccine shortage.

The JCVI endorsed this approach to maximise the number of doses that can be administered without compromising immunity. As a result of this endorsement, UKHSA updated their recommendations for the use of pre and post-exposure vaccination during a monkeypox incident.

Updated advice, September 2022

The JCVI was asked to consider how these remaining doses due to be delivered in August and September 2022 should be allocated, including whether vaccination of the highest-risk group with second doses should be prioritised or whether the priority is to expand the groups eligible for first doses.

Early feedback from the intradermal administration pilot suggests that 4 doses can be obtained from each vial, and that not all clinics would be able to offer intradermal vaccination. It is anticipated that offering widespread intradermal vaccination would allow up to a 3-fold increase in the number of people that can be offered vaccine.

With the current MVA-BN vaccine supply, it is considered likely that the offer of widespread intradermal vaccination would allow to either vaccinate the groups at highest risk with 2 doses, or to expand eligibility to those at lower risk, but with a single dose. However, it is unlikely there will be enough doses to vaccinate all of those at a lower risk of exposure.

UKHSA has run modelling to estimate the impact of prioritising vaccination of the highest-risk group with 2 doses, compared with prioritising expansion of vaccination with a single dose to a wider group.

This modelling suggests that the choice of vaccination strategy (offering second doses to those at highest risk, compared with offering single doses to a wider risk group) makes little difference to the outbreak size and duration. Offering second doses to the existing high-risk eligible group completes their primary course, thus maximising their direct protection and indirect protection via their contribution to current and future transmission.

Additionally, this approach may be operationally more feasible since this group has established links with sexual health services and may be identified using existing eligible proxies. This approach would likely result in some vaccine doses remaining available for use in outbreaks. Offering wider vaccination to those at intermediate risk of exposure could contribute to preventing further transmission. However, clear criteria for ‘intermediate risk’ should be considered if the epidemiology necessitates expanded vaccination.

The JCVI endorses UKHSA’s proposal to prioritise the offer of 2 doses to those in the existing target groups for pre-exposure vaccination (GBMSM at highest risk, and occupational vaccination) including efforts to maximise uptake of dose one within this group through engagement activities. Those at highest risk of exposure have an expectation that they will be offered 2 doses of vaccine.

It is estimated that, with plans for rolling out of intradermal vaccination, there should be more doses than required for the cohort identified. Therefore, once 2 doses of vaccine have been offered to those identified as being at high risk and uptake has plateaued, it may be reasonable to offer a single dose to those who are considered to be at an ‘intermediate’ risk of exposure to help increase resilience against further transmission.

The JCVI recognises the cost implications and impact on delivery capacity that recommending the widening of the offer may have. Due to the marginal difference between the different vaccination strategies, the timing and feasibility of this wider offer should be considered based on evolving epidemiology.

The JCVI will continue to review the ongoing outbreak and issue updated advice if required.