Past infection and vaccination protects against severe mpox

People with repeat mpox (formerly known as monkeypox) infections and those who were infected after vaccination appear less likely to develop severe illness, according to a global series of 37 cases reported in The Lancet Infectious Diseases.

These findings show that although people who had mpox can get it again, and vaccination does not always prevent infection, past infection and vaccines confer partial immunity that reduces the risk of complications. Individuals with second infections or post-vaccine infections had fewer mucosal lesions, were less likely to need pain medication and only one was hospitalised.

“Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature,” Professor Chloe Orkin of Queen Mary University of London and colleagues wrote. “Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series, both disease duration and severity appear to be reduced.”

“More than half of those in recent case clusters had previously had mpox or had been vaccinated.”

As aidsmap previously reported, the UK Health Security Agency (UKHSA) detected the first cases in a new global mpox outbreak in May 2022. As of 31 August 2023, UKHSA has identified 3782 cases in the UK. Worldwide, there have been nearly 90,500 as of 19 September, resulting in 157 deaths, according to the World Health Organisation. Case numbers have declined dramatically since last year’s peak, though sporadic small clusters are still being reported (since January, there have been 50 cases in the UK). Most mpox cases outside of Africa have been among gay, bisexual and other men who have sex with men.

To learn more about the global mpox outbreak, Orkin and a large team of colleagues formed an international collaboration known as the SHARE-net Clinical Group. The group previously published studies describing the spectrum of mpox symptoms, mpox cases among cisgender and transgender women and the severity of mpox among people with HIV.

In their latest report, the group analysed epidemiological and clinical characteristics of mpox among people with past infections or vaccination in an effort to better understand the disease in the setting of previous immunity.

Mpox is an orthopoxvirus closely reIated to smallpox, and the same vaccines provide protection against both viruses. 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.

Previous infection or vaccination is thought to confer lifelong immunity against smallpox, the study authors noted as background. However, recent studies have yielded widely varying estimates of mpox vaccine effectiveness, and more than half of those in recent case clusters in Europe and the United States had previously had mpox or had been fully or partially vaccinated.

For this case series, collaborators from nine countries provided data on people with PCR-confirmed mpox after a documented previous infection or more than 14 days after full vaccination. People who were partially vaccinated or who had received doses prior to the global outbreak were excluded.

All 37 individuals included in the case series were cisgender gay, bisexual or other men who have sex with men. Seven were reinfected, 29 had received two appropriately spaced doses of the MVA-BN vaccine, and one was both vaccinated and reinfected.

Of the eight repeat infections, three were from Europe (France and Italy) and five were from the Americas (Argentina, Canada, Mexico and the US). Of the 30 infections after vaccination, 13 were from Europe (France, Israel, Spain and the UK) and 17 were from the US.

Looking at reinfections and post-vaccination infections together, the median age was 36 years. About three quarters were White, 11% were Hispanic or Latino, 8% were Asian and 5% were Black. Consistent with prior studies, most reported condomless sex with multiple male partners. Nearly a third had one or more other sexually transmitted infections at the time of their most recent mpox diagnosis.

Eight men (22%) were living with HIV, and 83% of HIV-negative men were taking pre-exposure prophylaxis (PrEP). Among those with HIV, all were on antiretroviral therapy with an undetectable viral load. The median CD4 cell count was 555 and the median nadir (lowest-ever) count was 355. As recently reported, people with HIV are not more likely to develop severe mpox unless they have advanced immune suppression.

Among men with repeat mpox infections, the median time between infections was 16 weeks. Among the 30 men who were vaccinated, 14 had received two subcutaneous MVA-BN doses, eight received two intradermal doses and eight received one of each. The median time between the completion of vaccination and infection was 31 weeks. The HIV-negative man who was both vaccinated and reinfected was first infected just four days after his first vaccine dose and again 38 weeks later.

To describe the degree of illness, the study authors used the Mpox Severity Score System (Mpox-SSS), which takes into account the number and extent of sores, the presence of confluent or combined lesions, bacterial superinfection, how much mucosal area is affected, the level of required care and the need for pain medication.

Men who were reinfected or infected after vaccination had fewer and less severe sores that healed more quickly. Two men with repeat infections (25%) and 12 who were vaccinated (40%) had only a single ulcer. Men who were reinfected had a median of 10 lesions during their first bout of mpox, which fell to five during their second infection; vaccinated men had a median of just two lesions. Most men had sores on the chest or limbs, and anal-genital and oral lesions were common. Two vaccinated men required treatment with tecovirimat (TPOXX), including one who was hospitalised for a necrotising neck lesion.

Among the reinfected men, the median Mpox-SSS score decreased from 7.0 during their first infection to 5.5 during the second, while vaccinated men had a median score of 5.0. The lower score was primarily driven by less need for pain medication.

The clinical presentation of repeat infections and infections after vaccination appeared to differ from initial infections reported in 2022. Those cases were often characterised by severely painful anal mucosal lesions or debilitating mouth or throat lesions. There were no deaths in the new cohort and all but one were managed as outpatients. In contrast, around 10% of cases reported in 2022 required hospitalisation, often for higher-level pain medication or treatment of bacterial superinfections.

“Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection,” the researchers wrote.

Find out more: Mpox (monkeypox) and HIV

As limitations of this analysis, the researchers noted that this series included only PCR-confirmed symptomatic cases, and people with minimally symptomatic or asymptomatic repeat or post-vaccine infections might have been missed. What’s more, the men were not tested for antibodies to see if they had actually developed immunity, nor was their virus sequenced to determine if assumed repeat infections might have been relapses.

“Consistent and clear interventions developed with and for affected communities to improve vaccination uptake are vital, as is further research to better understand vaccine effectiveness in preventing infection,” the researchers concluded. “Above all, ensuring equity of access to vaccines and treatments, specifically to geographical areas historically affected by mpox, must be prioritised if we aim to end this global outbreak and ensure elimination of human-to-human mpox transmission.”