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Clin. Vaccine Immunol. doi:10.1128/CVI.00148-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Monkeypox induced immunity and failure of childhood smallpox vaccination to provide complete protection

Poxvirus Program, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta Ga.; Emory Vaccine Center and Yerkes National Primate Research Center Emory University, Atlanta Ga.; Emory University School of Medicine, Atlanta Ga.

^* To whom correspondence should be addressed. Email: idamon{at}cdc.gov.

	Abstract

Following the U.S. monkeypox outbreak of 2003, blood specimens, clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of pre-existing (smallpox vaccine-derived) and acquired immunity in susceptibility to monkeypox disease and clinical outcomes. Orthopoxvirus-specific IgG and IgM, and CD4, CD8 and B cell responses were measured at 7-14 weeks and one year post exposure. Associations between immune responses, smallpox vaccination, epidemiologic and clinical data were assessed. Participants were categorized into four groups; 1) vaccinated cases 2) unvaccinated cases 3) vaccinated contacts and 4) unvaccinated contacts. Cases, regardless of vaccination status, were positive for orthopoxvirus-specific IgM, IgG, CD4, CD8 and B cell responses. Anti-orthopoxvirus immune responses consistent with infection were observed in some contacts that did not develop monkeypox. Vaccinated contacts maintained low levels of anti-orthopoxvirus IgG, CD4 and B cell responses, with most lacking IgM or CD8 responses. Pre-existing immunity, assessed by high anti-orthopoxvirus IgG levels and childhood smallpox vaccination, was associated (in a non-significant manner) with mild disease. Vaccination failed to provide complete protection against human monkeypox. Previously vaccinated monkeypox cases manifested anti-orthopoxvirus IgM, and changes in anti-orthopoxvirus IgG, CD4, CD8 or B cell responses as markers of recent infection. Anti-orthopoxvirus IgM and CD8 responses occurred most frequently in monkeypox cases (vaccinated and unvaccinated), with IgG, CD4 and memory B cell responses indicative of vaccine derived immunity. Immune markers provided evidence of asymptomatic infections in some vaccinated, as well as unvaccinated, individuals.