Following the U.S.
monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of preexisting (
smallpox vaccine-derived) and acquired immunity in susceptibility to
monkeypox disease and clinical outcomes. Orthopoxvirus-specific
immunoglobulin G (
IgG),
IgM, CD4, CD8, and B-cell responses were measured at approximately 7 to 14 weeks and 1 year postexposure. Associations between immune responses,
smallpox vaccination, and epidemiologic and clinical data were assessed. Participants were categorized into four groups: (i) vaccinated cases, (ii) unvaccinated cases, (iii) vaccinated contacts, and (iv) unvaccinated contacts. Cases, regardless of vaccination status, were positive for orthopoxvirus-specific
IgM,
IgG, CD4, CD8, and B-cell responses. Antiorthopoxvirus immune responses consistent with
infection were observed in some contacts who did not develop
monkeypox. Vaccinated contacts maintained low levels of antiorthopoxvirus
IgG, CD4, and B-cell responses, with most lacking
IgM or CD8 responses. Preexisting immunity, assessed by high antiorthopoxvirus
IgG levels and childhood
smallpox vaccination, was associated (in a nonsignificant manner) with mild disease. Vaccination failed to provide complete protection against human
monkeypox. Previously vaccinated
monkeypox cases manifested antiorthopoxvirus
IgM and changes in antiorthopoxvirus
IgG, CD4, CD8, or B-cell responses as markers of recent
infection. Antiorthopoxvirus
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.