Gay and bisexual men urged to get vaccinated against mpox as new cases reported

As clusters of new mpox (formerly monkeypox) are reported in cities including London and Chicago, health officials are urging gay and bisexual men and transgender people to get vaccinated -- or to get their second dose if they’ve had only one.

“It is clear from these latest statistics that mpox has not gone away,” Dr Katy Sinka, head of sexually transmitted infections at the UK Health Security Agency (UKHSA), said in a press statement. “Vaccination is key to reducing the severity of symptoms and preventing further transmission. Uptake of first doses has been strong but only around a third of those who have received their first dose have had their second dose so far.”

Mpox cases have declined dramatically since the outbreak peaked late last summer, likely due to a combination of behaviour change, vaccination and natural immunity after infection. In many countries hit hard by last year’s outbreak, weekly cases reached zero in late 2022 or early 2023. But the recently reported clusters prompt concern that mpox could return this summer if vaccination rates remain low.

Health authorities in France reported a cluster of 17 mpox cases in the Centre-Val de Loire region in March, but this was not followed by a further rise in April, suggesting the outbreak is contained. In Chicago, the health department reported 31 cases starting in late April, but only one case was reported during the week ending 27 May. In the UK, 20 cases have been reported this year, half of them in London in May.

Across these three clusters, most cases were among men who have sex with men. What’s more, a majority had received one or two mpox vaccine doses, raising questions about how well the vaccines work and for how long.

Vaccine effectiveness

Mpox is related to smallpox, and vaccines developed to prevent smallpox also protect against mpox. The MVA-BN vaccine, sold as Imvanex in Europe and Jynneos in the US, was deployed in several countries during the 2022 outbreak, first as a subcutaneous injection and later -- in an effort to stretch the limited supply -- as an intradermal injection using one-fifth the original dose. Both administration methods require two doses given about four weeks apart.

A series of recent studies provide a wide range of estimates of vaccine effectiveness. They reported lower effectiveness with single doses than with two doses, while two also found that people living with HIV or another immunocompromising condition had less protection than others.

At this year’s Conference on Retroviruses and Opportunistic Infections, researchers reported that first, second and third generation smallpox vaccines protect against mpox infection. Among participants in the French DoxyVAC trial, a single dose of the MVA-BN vaccine was found to be 99% effective.

In another study, published in The Lancet Infectious Diseases, Marta Betran of UKHSA and colleagues assessed the effectiveness of the first MVA-BN dose for at-risk gay, bisexual and other men who have sex with men. This analysis included 363 men who developed mpox symptoms between 4 July and 9 October 2022. Of these, 323 were unvaccinated, 32 cases occurred within 13 days after vaccination – when immunity would still be incomplete – and just eight occurred two weeks or more after the first vaccine dose. The estimated vaccine effectiveness 14 days after one dose was 78%, leading the study authors to conclude that a single MVA-BN dose was “highly protective.”

But other studies have not seen such high effectiveness, especially with only one dose.

In a study described in Morbidity and Mortality Weekly Report, researchers with the US Centers for Disease Control and Prevention (CDC) and several city and state health departments conducted a case-control comparison of sexually active men who have sex with men and transgender individuals ages 18 to 49 in 12 US jurisdictions. Between 19 August 2022 and 31 March 2023, a total of 309 people with confirmed or probable mpox were matched to 608 people seen at sexual health or HIV clinics who did not have a mpox diagnosis. Mpox exposure, diagnosis, vaccination status and presence of HIV and other immunocompromising conditions were self-reported. Overall, 23% of the participants were fully vaccinated with two MVA-BN doses, 32% were partially vaccinated with a single dose and 45% were unvaccinated.

After adjusting for age, race/ethnicity, immunocompromised status and close contact with a person with known or suspected mpox, vaccine effectiveness was 75% for one dose of MVA-BN and 86% for two doses. According to the study authors, the vaccine provided “substantial” and “comparable” protection regardless of administration method or immunocompromised status.

However, there were some notable differences. Vaccine effectiveness was 89% for people who received two subcutaneous MVA-BN doses, 80% for those who got two intradermal doses and 87% for those who received one of each. On the other hand, among those who only got one dose, effectiveness was 77% for subcutaneous injection versus 81% for intradermal administration.

While vaccine effectiveness was 72% with one dose and 88% with two doses for people with a healthy immune system, this fell to 51% and 70%, respectively, for immunocompromised people. Although these estimates did not differ statistically, the study authors acknowledged that immunocompromised people might have “a less robust response” to the vaccine.

In a second study described in the same edition, Dr Eli Rosenberg of the New York State Department of Health and colleagues compared 252 men age 18 and older who were diagnosed with mpox in New York state, excluding New York City, from 24 July to 31 October 2022 and 255 men diagnosed with rectal gonorrhoea or primary syphilis but not mpox.

The study authors noted that this method better controls for confounding factors because both groups were at risk for sexually transmitted infections (STIs) and sought testing. Other studies that include people at lower risk for mpox could have inflated estimates of vaccine effectiveness.

Of the 252 men with mpox, 10 had received a single dose of the MVA-BN vaccine less than two weeks prior to diagnosis, 10 had received one dose at least 14 days prior and only two were fully vaccinated. Among the 255 men in the control group, 23 had received one dose and 19 had received two doses 14 days or more prior to their STI diagnosis. In this analysis, the adjusted vaccine effectiveness was 68% for one vaccine dose and 89% for two doses. No effectiveness was observed if the single dose was administered less than 13 days prior to mpox diagnosis.

In a third study, published in the New England Journal of Medicine, Dr. Nicholas Deputy of the CDC’s Mpox Emergency Response Team and colleagues conducted a case-control comparison using data from Cosmos, a US nationwide electronic health record database. Of note, a large proportion of the study population was immunocompromised.

"While vaccination may not offer complete protection against mpox infection or reinfection, it is likely to prevent severe illness."

The 2193 case patients had a recorded mpox diagnosis code or a positive mpox or orthopox virus lab test between 15 August and 19 November 2022. The 8319 control participants were newly diagnosed with HIV or had a new or refill PrEP prescription. Of these, 25 case patients and 335 control participants received two doses of the MVA-BN vaccine while 146 and 1000, respectively, got a single dose.

Here, the estimated adjusted vaccine effectiveness was 36% with one dose and 66% with two doses – substantially lower than the effectiveness seen in the previous two studies. However, among people who were not immunocompromised, vaccine effectiveness increased to 41% with one dose and 76% with two doses.

The variability in these effectiveness estimates is likely attributable to different populations, different data sources and varying degrees of self-selection bias. However, the estimates are generally within each others’ confidence intervals, meaning they are statistically similar, Dr Christopher Braden, CDC’s mpox response incident manager, said during a May 18 media briefing.

Considering when these studies were conducted, they cannot say much about how long vaccines remain effective. It is not clear whether people who became infected after vaccination in the recent clusters never achieved full protection or if protection waned over time. Alternative explanations might include mpox virus mutation or improper vaccine administration, according to White House’s national mpox response deputy coordinator Dr Demetre Daskalakis.

Health officials and advocates stress the importance of getting both vaccine doses. Even people who previously had mpox are advised to get vaccinated, as there have been several reported cases of reinfection. People who develop symptoms suggestive of mpox should get tested even if they are fully vaccinated or recovered.

In the UK, people who have not yet received two doses of the vaccine are urged to book their first dose by 16 June and their second dose by the end of July 2023, as the vaccination programme is scheduled to wind down. [Update: on 16 June, UKHSA announced that the programme would continue in London, due to the extra cases in the city].

While vaccination may not offer complete protection against mpox infection or reinfection, it is likely to prevent severe illness. All cases in the recent Chicago cluster were mild and no one required treatment. Plus, the more people who are vaccinated, the less mpox will circulate in communities.

“Vaccination makes getting and spreading mpox less likely and may decrease the chances of severe illness, hospitalization and death,” Daskalakis said during the briefing. “[T]hough no vaccine is perfect, even imperfect immunity in many people means a lot of immunity in the population, and the result is that we are less likely to have outbreaks.”
 
Full vaccination is especially important for people with advanced HIV, who are more prone to developing severe mpox illness. Along with vaccination, starting and staying on antiretroviral therapy can reduce the risk for serious mpox complications.

It is not yet clear whether mpox vaccine boosters could increase or extend the duration of protection. While further studies are underway, UK and US health officials do not recommend booster jabs at this time.