Specificity of immunoglobulin M and G antibody responses in humans infected with eastern and western equine encephalitis viruses: application to rapid serodiagnosis

Abstract

Paired sera from 20 humans with eastern equine encephalitis (EEE) virus infections and from 17 humans with western equine encephalitis (WEE) virus infections, all with previously demonstrated fourfold or greater rises or falls in hemagglutination-inhibiting, complement-fixing, or neutralizing antibody titers, were tested for immunoglobulin M (IgM) and IgG antibodies by an enzyme immunoassay. All individuals with EEE and 14 of 17 individuals with WEE had IgM antibody, some as early as 1 day after onset. Two of the three persons with WEE who did not develop IgM antibody died. IgM antibody declined but persisted for at least 3 months after the onset of illness in one individual each with EEE and WEE. IgG antibody was not detected until the middle of week 2 after onset. The sensitivity of the IgM antibody capture enzyme immunoassay described and the specificity, as shown by the absence of heterologous alphavirus reactivity, indicate that this is the test of choice for the rapid diagnosis of human infections caused by EEE and WEE viruses.

The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation

“…The nature of the immunosuppressive agents may contribute to this difference; following pneumococcal vaccine challenge, rituximab has a clear association with an impaired antibody response ( van Aalst et al, 2018 ) whereas solid organ transplant recipients on immunosuppression develop antibody levels comparable to healthy controls ( Dendle et al, 2018 ). The antibody titers observed in this instance of transplant-associated EEEV infection are in line with those from two individual case reports in immunocompetent hosts, although the IgM titers are lower than those reported in two case series ( Calisher et al, 1986a , b ; Golomb et al, 2001 ; Garlick et al, 2016 ). Due to biosafety limitations, specimens from early time points post-infection could not be obtained, although previously published testing reported this individual had detectable serum IgM and neutralizing antibodies present as early as 9 days post-transplantation ( Pouch et al, 2018 ).…”

“…IgG antibodies to EEEV have been documented as early as 10-11 days after symptom onset in previous cases (Calisher et al, 1986a), unfortunately early specimens were not available from this individual to assess when the IgG response began although rising IgG titers were demonstrated between DOI 39 and DOI 48. No cross-neutralization of WEEV or VEEV were observed despite very high levels of EEEV neutralizing antibodies.…”

Detection of Anti-Arboviral Immunoglobulin G by Using a Monoclonal Antibody-Based Capture Enzyme-Linked Immunosorbent Assay

“…Analysis of anti-arboviral IgG in patient sera by using the ELISA format has previously been reported (2). When inactivated antigens are applied as a coating directly onto a plate, nonspecific background reactions occur (7).…”

“…Previous publications have described the rapid diagnosis of individual medically important arboviral infections with ELISA (2,3,15). Some of these procedures have been adapted and incorporated into comprehensive sets of assays for the detection of anti-arboviral immunoglobulin M (IgM) (IgM antibody-capture [MAC]-ELISA) (14).…”

Medically important arboviruses of the United States and Canada.

“…As detected by IgM antibody capture ELISA (MACELISA), IgM antibody to each of these viruses crossreacts with heterologous viruses of the same group but is most reactive with other viruses of the same antigenic complex (36,37,44,47,170,196). For example, IgM antibody from patients with LAC virus infection has highest titers to LAC virus itself, but it also reacts to a lesser extent with snowshoe hare virus and to a still lesser extent with Jamestown Canyon virus.…”