1887
  1. Home
  2. Eurosurveillance
  3. Volume 31, Issue 14, 09/Apr/2026
  4. Article
Research Open Access
Like 0
Download

2025 theme: Vaccines

Abstract

BACKGROUND

Monkeypox virus (MPXV) has spread globally to non-endemic countries in recent years and has the potential to cause recurrent outbreaks. Vaccine breakthrough infections and reinfections are suggested to be linked to immunity waning over time.

AIM

We aimed to determine how long individuals remain protected following MPXV infection and if vaccination can be used as a public heath measure to elicit durable protective immune responses.

METHODS

This retrospective observational study investigated the durability of humoral immune responses in a longitudinal cohort of 46 individuals infected with MPXV during the 2022 global mpox outbreak. We collected 86 blood samples up to 7 months after infection, and analysed the antibody responses against MPXV with a serological assay using a panel of eight viral antigens.

RESULTS

Monitoring of antibody kinetics revealed transient IgM responses in the first weeks following infection and a robust polyclonal IgG response that peaked 1–2 months after infection but declined consistently in the following months. Post-exposure immunisation with third-generation modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine did not seem to increase significantly the strength, breadth or longevity of antibody responses. Using a separate cohort of 25 uninfected long-term MVA-BN vaccinees, we observed low to undetectable seropositivity against most MPXV antigens after 30 months.

CONCLUSION

As circulating antibody titres have been identified as a correlate of protection against mpox, declining antibody levels raise concerns for mpox susceptibility in previously infected and vaccinated persons. This warrants further evaluation of long-term vaccine effectiveness to inform booster vaccination guidance.

© Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2026.31.14.2500479
2026-04-09
2026-05-10
/content/10.2807/1560-7917.ES.2026.31.14.2500479
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/31/14/eurosurv-31-14-1.html?itemId=/content/10.2807/1560-7917.ES.2026.31.14.2500479&mimeType=html&fmt=ahah

References

  1. Gessain A, Nakoune E, Yazdanpanah Y. Monkeypox. N Engl J Med. 2022;387(19):1783-93.  https://doi.org/10.1056/NEJMra2208860  PMID: 36286263 
  2. World Health Organization (WHO). Global mpox trends. Geneva: WHO. [Accessed: 30 Apr 2025]. Available from: https://worldhealthorg.shinyapps.io/mpx_global
  3. Rimoin AW, Mulembakani PM, Johnston SC, Lloyd Smith JO, Kisalu NK, Kinkela TL, et al. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc Natl Acad Sci USA. 2010;107(37):16262-7.  https://doi.org/10.1073/pnas.1005769107  PMID: 20805472 
  4. Nguyen PY, Ajisegiri WS, Costantino V, Chughtai AA, MacIntyre CR. Reemergence of human monkeypox and declining population immunity in the context of urbanization, Nigeria, 2017-2020. Emerg Infect Dis. 2021;27(4):1007-14.  https://doi.org/10.3201/eid2704.203569  PMID: 33756100 
  5. Voigt EA, Kennedy RB, Poland GA. Defending against smallpox: a focus on vaccines. Expert Rev Vaccines. 2016;15(9):1197-211.  https://doi.org/10.1080/14760584.2016.1175305  PMID: 27049653 
  6. World Health Organization (WHO). Smallpox and mpox (orthopoxviruses): WHO position paper, August 2024. Geneva: WHO. 2024. Available from: https://www.who.int/publications/i/item/who-wer-9934-429-456
  7. Pischel L, Martini BA, Yu N, Cacesse D, Tracy M, Kharbanda K, et al. Vaccine effectiveness of 3rd generation mpox vaccines against mpox and disease severity: A systematic review and meta-analysis. Vaccine. 2024;42(25):126053.  https://doi.org/10.1016/j.vaccine.2024.126409  PMID: 39413490 
  8. Mason LMK, Betancur E, Riera-Montes M, Lienert F, Scheele S. MVA-BN vaccine effectiveness: A systematic review of real-world evidence in outbreak settings. Vaccine. 2024;42(26):126409.  https://doi.org/10.1016/j.vaccine.2024.126409  PMID: 39413490 
  9. World Health Organization (WHO). Smallpox and mpox (orthopoxviruses) vaccine position paper, August 2024. World Health Organization; 2024 [cited 2025 May 14]. Available from: https://www.who.int/publications/i/item/who-wer-9934-429-456
  10. Berry MT, Khan SR, Schlub TE, Notaras A, Kunasekaran M, Grulich AE, et al. Predicting vaccine effectiveness for mpox. Nat Commun. 2024;15(1):3856.  https://doi.org/10.1038/s41467-024-48180-w  PMID: 38719852 
  11. Edghill-Smith Y, Golding H, Manischewitz J, King LR, Scott D, Bray M, et al. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat Med. 2005;11(7):740-7.  https://doi.org/10.1038/nm1261  PMID: 15951823 
  12. Kottkamp AC, Samanovic MI, Duerr R, Oom AL, Belli HM, Zucker JR, et al. Antibody titers against mpox virus after vaccination. N Engl J Med. 2023;389(24):2299-301.  https://doi.org/10.1056/NEJMc2306239  PMID: 38091537 
  13. Lim SY, Kim HS, Yim HS, Kim H, Han IA, Yoon D, et al. Comparison of waning antibody responses after natural monkeypox virus infection and mpox vaccination beyond 6 months in South Korea. Open Forum Infect Dis. 2024;11(10):ofae566.  https://doi.org/10.1093/ofid/ofae566  PMID: 39450396 
  14. Collier AY, McMahan K, Jacob-Dolan C, Liu J, Borducchi EN, Moss B, et al. Decline of mpox antibody responses after Modified Vaccinia Ankara-Bavarian Nordic vaccination. JAMA. 2024;332(19):1669-72.  https://doi.org/10.1001/jama.2024.20951  PMID: 39361499 
  15. Hicks B, Jones S, Callaby H, Bailey D, Gordon C, Rampling T, et al. Evaluation of a multiplexed immunoassay for assessing long-term humoral immunity orthopoxviruses. Vaccine. 2024;42(26):126453.  https://doi.org/10.1016/j.vaccine.2024.126453  PMID: 39426286 
  16. Phipps K, Yates J, Pettit J, Bialosuknia S, Hunt D, DuPuis AP 2nd, et al. Short-lived neutralizing antibody responses to monkeypox virus in smallpox vaccine-naive persons after JYNNEOS vaccination. Emerg Infect Dis. 2025;31(2):237-45.  https://doi.org/10.3201/eid3102.241300  PMID: 39793541 
  17. Oom AL, Wilson KK, Yonatan M, Rettig S, Youn HA, Tuen M, et al. The two-dose MVA-BN mpox vaccine induces a nondurable and low avidity MPXV-specific antibody response. J Virol. 2025;99(9):e0025325.  https://doi.org/10.1128/jvi.00253-25  PMID: 40162783 
  18. Selverian CN, Monticelli SR, Jaleta YM, Lasso G, DeMouth ME, Meola A, et al. Monkeypox virus infection stimulates a more robust and durable neutralizing antibody response compared to modified vaccinia virus Ankara vaccination. J Infect Dis. 2025;231(4):1069-73.  https://doi.org/10.1093/infdis/jiae515  PMID: 39422181 
  19. Liu WD, Chao TL, Chen KH, Sun HY, Lin KY, Chuang YC, et al. Short-term evolution of Mpox-specific IgG and neutralizing antibodies among individuals undergoing MVA-BN vaccination. Int J Infect Dis. 2025;153:107830.  https://doi.org/10.1016/j.ijid.2025.107830  PMID: 39894441 
  20. Guagliardo SAJ, Kracalik I, Carter RJ, Braden C, Free R, Hamal M, et al. Monkeypox virus infections after 2 preexposure doses of JYNNEOS vaccine - United States, May 2022-May 2024. MMWR Morb Mortal Wkly Rep. 2024;73(20):460-6.  https://doi.org/10.15585/mmwr.mm7320a3  PMID: 38781111 
  21. Hazra A, Zucker J, Bell E, Flores J, Gordon L, Mitjà O, et al. Mpox in people with past infection or a complete vaccination course: a global case series. Lancet Infect Dis. 2024;24(1):57-64.  https://doi.org/10.1016/S1473-3099(23)00492-9  PMID: 37678309 
  22. Li T, Li Z, Xia Y, Long J, Qi L. Mpox reinfection: A rapid systematic review of case reports. Infect Med (Beijing). 2024;3(1):100096.  https://doi.org/10.1016/j.imj.2024.100096  PMID: 38586545 
  23. Gilchuk I, Gilchuk P, Sapparapu G, Lampley R, Singh V, Kose N, et al. Cross-neutralizing and protective human antibody specificities to poxvirus infections. Cell. 2016;167(3):684-694.e9.  https://doi.org/10.1016/j.cell.2016.09.049  PMID: 27768891 
  24. Chang SJ, Chang YX, Izmailyan R, Tang YL, Chang W. Vaccinia virus A25 and A26 proteins are fusion suppressors for mature virions and determine strain-specific virus entry pathways into HeLa, CHO-K1, and L cells. J Virol. 2010;84(17):8422-32.  https://doi.org/10.1128/JVI.00599-10  PMID: 20538855 
  25. Townsend MB, Keckler MS, Patel N, Davies DH, Felgner P, Damon IK, et al. Humoral immunity to smallpox vaccines and monkeypox virus challenge: proteomic assessment and clinical correlations. J Virol. 2013;87(2):900-11.  https://doi.org/10.1128/JVI.02089-12  PMID: 23135728 
  26. Otter AD, Jones S, Hicks B, Bailey D, Callaby H, Houlihan C, et al. Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals. Nat Commun. 2023;14(1):5948.  https://doi.org/10.1038/s41467-023-41587-x  PMID: 37741831 
  27. CDC. Mpox Case Definitions | Mpox | CDC. 2024 [cited 2025 May 3]. Available from: https://www.cdc.gov/mpox/hcp/case-definitions/index.html
  28. Public Health Agency of Canada (PHAC). Smallpox and mpox vaccines: Canadian immunization guide. Ottawa: PHAC. [Accessed: 9 Jun 2025]. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-21-smallpox-vaccine.html
  29. Zuiani A, Dulberger CL, De Silva NS, Marquette M, Lu YJ, Palowitch GM, et al. A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease. Cell. 2024;187(6):1363-1373.e12.  https://doi.org/10.1016/j.cell.2024.01.017  PMID: 38366591 
  30. Mucker EM, Freyn AW, Bixler SL, Cizmeci D, Atyeo C, Earl PL, et al. Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates. Cell. 2024;187(20):5540-5553.e10.  https://doi.org/10.1016/j.cell.2024.08.043  PMID: 39236707 
  31. Hunt JH, Jones JL, Gebo KA, Hansoti B, Traut CC, Hamill MM, et al. Discordant performance of mpox serological assays. J Virol Methods. 2024;329:115004.  https://doi.org/10.1016/j.jviromet.2024.115004  PMID: 39127186 
  32. Dubois ME, Hammarlund E, Slifka MK. Optimization of peptide-based ELISA for serological diagnostics: a retrospective study of human monkeypox infection. Vector Borne Zoonotic Dis. 2012;12(5):400-9.  https://doi.org/10.1089/vbz.2011.0779  PMID: 22217169 
  33. Kobiyama K, Utsumi D, Kaku Y, Sasaki E, Yasui F, Okamura T, et al. Immunological analysis of LC16m8 vaccine: preclinical and early clinical insights into mpox. EBioMedicine. 2025;115:105703.  https://doi.org/10.1016/j.vaccine.2024.126409  PMID: 39413490 
  34. Adamo S, Gao Y, Sekine T, Mily A, Wu J, Storgärd E, et al. Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox. Cell Host Microbe. 2023;31(6):928-936.e4.  https://doi.org/10.1016/j.chom.2023.04.015  PMID: 37236191 
Waning humoral immunity following monkeypox virus infection and vaccination, Canada, 2020 to 2023
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=J%C3%A9r%C3%A9mie+Pr%C3%A9vost&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Prévost Jérémie</a>, <a href="/search?value1=Sarah+J+Medina&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Medina Sarah J</a>, <a href="/search?value1=Ana+Citlali+M%C3%A1rquez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Márquez Ana Citlali</a>, <a href="/search?value1=Kristina+Dimitrova&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Dimitrova Kristina</a>, <a href="/search?value1=Tahereh+Valadbeigy&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Valadbeigy Tahereh</a>, <a href="/search?value1=Gabrielle+Angelo+P+Cortez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Cortez Gabrielle Angelo P</a>, <a href="/search?value1=Mruthula+Narayan&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Narayan Mruthula</a>, <a href="/search?value1=William+C+Carson&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Carson William C</a>, <a href="/search?value1=Michael+B+Townsend&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Townsend Michael B</a>, <a href="/search?value1=Agatha+N+Jassem&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Jassem Agatha N</a>, <a href="/search?value1=David+Safronetz&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Safronetz David</a></span>. Waning humoral immunity following monkeypox virus infection and vaccination, Canada, 2020 to 2023. <a href="/content/ecdc">Euro Surveill.</a> 2026;31(14):pii=2500479. <a href="https://doi.org/10.2807/1560-7917.ES.2026.31.14.2500479" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2026.31.14.2500479</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 03 Jul 2025;&nbsp;&nbsp; <span class="generated">Accepted</span>: 05 Feb 2026 </span> </p>
/content/10.2807/1560-7917.ES.2026.31.14.2500479
/content/10.2807/1560-7917.ES.2026.31.14.2500479
Loading

Data & Media loading...

Supplementary data

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error