Tuesday, February 4, 2025

Research suggests booster doses may be needed for immunity against monkeypox


New research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, ​​Spain (April 27-30) shows that even in men who receive two doses of the mpox vaccine intradermally, Their level of antibodies against the virus drops to low or no levels in the first few months if they have not received a prior smallpox vaccine.

The authors, including Dr Klara Sonden, deputy epidemiologist at the Public Health Agency of Sweden and affiliated with the Karolinska Institute in Stockholm, Sweden, say their study shows that booster vaccination may be necessary over time. term for these people, and that scientific evidence is necessary to support any decision.

Since May 2022, an epidemic of mpox has emerged globally, spreading primarily among men who have sex with men (MSM). It has been classified as a public health emergency of international concern (PHEIC). In Sweden, a smallpox vaccine based on modified live Ankara vaccination virus (MVA-BN) was offered intradermally to at-risk groups. Intradermal administration means 0.1 ml into the skin, which is one-fifth of the dose needed for subcutaneous administration. This was used as a dose-saving strategy as supplies were initially limited.

The vaccine has been shown to be effective in studies using real-world data from the 2022 outbreak and beyond among MSM, with limited numbers of breakthrough infections and milder disease reported when breakthrough infections occur until now. The aim of this cohort study was to evaluate the dynamics and factors affecting neutralizing antibodies against mpox virus (MPXV) after MVA-BN vaccination.

A total of 100 MSM attending the “Venhälsan” sexual health clinic, Stockholm, Sweden, who were eligible to receive the MVA-BN vaccine, were included in the study. After the initial serum sample collected before dose 1, serum samples were collected before dose 2 and 28 days and three months after the second dose. These samples were tested to establish titers (levels) of MPXV-neutralizing antibodies. Titers were compared in individuals with or without previous smallpox vaccination and patients with previous natural infection were included as positive controls.

10 people had uncertain status regarding smallpox vaccination (due to being born in many different countries during the period 1977-1980 when vaccination declined globally) and 23 people had already been vaccinated against smallpox. The other 67 people had no history of smallpox vaccination.

A total of 312 samples from four time points from the 100 people included in the study were analyzed. In addition to the study population, age- and sex-matched anonymized controls from blood donors were included as negative controls (n = 20) and individuals previously infected with MPXV as positive controls (n = 20). . The controls each gave a blood sample.

Within the study group, prior smallpox vaccination was associated with significantly higher antibody titers, and 15/23 of these individuals had preexisting neutralizing antibodies (i.e., memory of B lymphocytes was still present thanks to their previous vaccination against smallpox).

Among those who had not previously been vaccinated against smallpox, less than half the group had detectable neutralizing antibodies 28 days after the second vaccination, with those who showed responses having a median titer (standard unit of measurement for antibodies) of 20. In contrast, for previously vaccinated individuals, the median titer 28 days after a single dose of MVA-BN vaccine was 40.

The authors say: “Our results support other studies showing that mpox vaccination results in neutralizing antibodies only in a proportion of vaccinated people, and that a significant decline already occurs during the first month after vaccination. Immunity after previous MPXV infection results in a higher and more robust neutralizing response. In conclusion, the results merit study of booster doses.

They continue: “Our results indicate a rapid decline in neutralizing antibodies after two doses and are consistent with other recent studies. These results, along with the continued spread of mpox in MSM populations in Europe, prompted consideration of a booster dose. a recommendation must be based on scientific evidence. However, to our knowledge, no clinical trials have studied or are studying a 3rd dose of MVA-BN (based on a Clinicaltrials.gov analysis from March 2024), but a booster dose is common. practical for inactivated vaccines. The MVA-BN is a live, non-replicating vaccine and therefore probably equivalent to an inactivated vaccine. The studies are essential to inform public health policy, and Sweden’s largest STI clinic plans to carry out a randomized clinical trial of a booster dose with immunological parameters as the primary outcome in comparison with those who received both doses of the regular complete treatment. 0.5 subcutaneous (sc) dose (0.5 ml), two doses of the intradermal dose-sparing dose (id) (0.1 ml), or one sc dose/one id dose, and those without a booster dose.”

They add that despite this, the Smallpox cases in Sweden have been few and mostly imported in 2023 (12 cases) and 2024 (5 cases) and the vast majority involved unvaccinated people. Data collection is ongoing regarding the occurrence of breakthrough infections in Sweden. Breakthrough cases have been reported in the scientific literature in individuals who received different vaccination strategies (i.e. sc/sc, id/sc, id/id) (Hazra et al).

The results presented here indicate that long-term protective immunity may require a booster dose for its maintenance. Since the current situation regarding mpox in Sweden is stable and transmission is minimal, any policy changes must be supported by clinical trial results. Currently, we will focus on finding unvaccinated people who are at risk of contracting mpox and offering them vaccination, and we believe that this together with previously administered vaccinations will help reduce the risk of further mpox outbreaks in Sweden in the future. future.


Dr. Klara Sonden, deputy state epidemiologist



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