Mpox breakthrough cases after two doses of the MVA-BN vaccine

1 November 2024. Related: Early access, mpox (monkeypox).

Simon Collins, HIV i-Base

A research letter reporting a severe case of mpox despite having previously received two doses of the MVA-BN vaccine also usefully reviews other breakthrough cases. [1]

These have sometimes been reported in people with reduced immune responses linked to advanced HIV or other complications. However, other cases have been reported in people with good CD4 counts, independently of HIV.

The initial case report was a 36 year old Taiwanese man who had been on suppressive ART with viral load <20 copies/mL for nine years and a current CD4 count of 579 cells/mm³. The MVA-BN vaccine had been given 11 and 16 months previously.

An in-house ELISA for titres of two mpox-associated proteins (anti-A29 and anti-H3L IgG) were 1:200 and 1:400, respectively. However, archived serum samples taken one month after each previous vaccination showed negative results, suggesting failed immune responses. CD4 counts 1-2 months after each vaccination were also high, roughly 840 and 450 cells/mm³, respectively.

The review of other breakthrough infections included:

• Non response due to concurrent use of corticosteroids and IL-5 monoclonal therapy for asthma. [2]
• Non response in two HIV negative men also linked to negative IgG and IgM. [3]
• More frequent sexual exposure. [4, 5, 6]

In the initial reported case, tecovirimat (600 mg twice daily) was started on the second hospital day in addition to intravenous acyclovir and metronidazole and intramuscular administration of ceftriaxone of 500 mg, followed by a 7-day course of doxycycline. He was discharged with oral tecovirimat and paromomycin. All blisters resolved two weeks after completing a 14-day course of tecovirimat.

References

1. Liu W-D et al. Serum Mpox-specific IgG titers before and after breakthrough Mpox infection in an HIV-infected individual with viral suppression and prior 2-dose Mpox vaccination. Letter. Journal of Microbiology, Immunology and Infection. (22 October 2024).
   https://doi.org/10.1016/j.jmii.2024.10.003
2. Bottanelli M et al. A case of breakthrough mpox infection in an individual non-responder to MVA-BN vaccination. Lancet Infect Dis, 24 (2024), pp. e11-e12.
   https://www.sciencedirect.com/science/article/pii/S1473309923007417
3. Weerasinghe MN et al. Breakthrough mpox despite two-dose vaccination. Med J Aust, 219 (2023), pp. 295-296.
   https://onlinelibrary.wiley.com/doi/epdf/10.5694/mja2.52076
4. Taha AM et al. Mpox breakthrough infections: concerns and actions. Lancet Infect Dis, 23 (2023), pp. 1216-1218.
   https://www.sciencedirect.com/science/article/pii/S1473309923005467
5. Merad Y et al. Outcomes of post-exposure vaccination by modified vaccinia Ankara to prevent mpox (formerly monkeypox): a retrospective observational study in Lyon, France, June to August 2022. Euro Surveill, 27 (2022), Article 2200882.
   https://pubmed.ncbi.nlm.nih.gov/36695469/
6. Jiang W et al. Breakthrough infection and reinfection in patients with Mpox. Rev Med Virol, 34 (2024), Article e2522.
   https://pubmed.ncbi.nlm.nih.gov/38348583/