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Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox


Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with ≥95% sensitivity and ≥90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.

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Figure 1: Antiviral antibody responses after orthopoxvirus infection.
Figure 2: Diagnosis of recent monkeypox infection by quantification of orthopoxvirus-specific T cells.
Figure 3: Analysis of monkeypox-specific peptide ELISAs for diagnosing monkeypox infection.
Figure 4: Relationship between reported and unreported (that is, asymptomatic) monkeypox infections.

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We thank the many volunteers for the gifts of their time and participation in this research study. We also thank M.B. Graham and J. Fairley for discussions and H.-P. Raué for help with manuscript preparation. This work was supported in part by Public Health Service grant 5 MO1 RR00334 and Oregon National Primate Research Center grant RR00163 (to M.K.S.).

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Correspondence to Mark K Slifka.

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Oregon Health & Science University, Mark K. Slifka, Paul Yoshihara and Erika Hammarlund have a financial interest in Najít Technologies, Inc., a company that may have a commercial interest in the results of this research and technology. This potential conflict was disclosed to the Oregon Health & Science University Conflict of Interest in Research Committee and an approved management plan was implemented.

Supplementary information

Supplementary Fig. 1

Comparison of the number of monkeypox lesions reported by unvaccinated and vaccinated monkeypox patients. (PDF 43 kb)

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Hammarlund, E., Lewis, M., Carter, S. et al. Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat Med 11, 1005–1011 (2005).

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