Development of antibody biomarkers of long term and recent dengue virus infections

Abstract

Dengue virus (DENV) infections elicit antibody responses to the non-structural protein 1 (NS1) that are associated with protection against disease. However, the antibody isotypes and subclasses involved, and their kinetics have not been extensively studied. We characterized the antibody responses to DENV NS1 by enzyme-linked immunosorbent assay (ELISA) in a longitudinal cohort of 266 confirmed dengue cases in Recife, Northeast Brazil. Samples were collected during the febrile phase and up to over 3 years after onset of symptoms. The antibodies investigated [IgA, IgM, total IgG (all subclasses measured together) and each subclass (IgG2, IgG3 and IgG4) measured separately] had distinct kinetic profiles following primary or secondary DENV infections. Of interest, most of these antibodies were consistently detected greater than 6 months after onset of symptoms, except for IgG3. Anti-dengue NS1-specific IgG was consistently detected from the acute phase to beyond 3 years after symptom onset. In contrast, anti-dengue NS1-specific IgG3 was detected within the first week, peaked at week 2-3, and disappeared within 4-6 months after onset of symptoms. The mean duration of the IgG3 positive signal was 149 days (ranging from 126 to 172 days). In conclusion, anti-dengue NS1-specific IgG and IgG3 are potential biomarkers of long-term and recent (less than 6 months) DENV infections, respectively.

Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region

“…We investigated potential associations between DENV antibody titers measured before the ZIKV epidemic and the subsequent risk of ZIKV infection. A total of 642 samples collected in March 2015 were tested for total IgG against DENV NS1 protein, a marker of prior DENV infection; 553 samples (86%) were positive (30). Age-specific seropositivity patterns were consistent with high levels of endemic DENV transmission in this population (Fig.…”

Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses

“…Among adults with dengue virus infection in Taiwan, 71% (31 of 44) had IgM antibodies against the envelope protein detectable at 6 months after acute infection, and 46% (20 of 44) had detectable IgM at 12 months after onset (49). Among 266 patients from Brazil with confirmed dengue virus infection, >70% had IgM antibody against the NS1 protein detected for >90 days after illness onset (49,50). In one study of patients with symptomatic Zika virus infection, 87% (52 of 60) had detectable IgM antibodies >60 days after symptom onset (5).…”

“…Neutralizing antibodies persist for multiple years after flavivirus infections and usually confer long-lived immunity (52)(53)(54). In persons previously infected with or vaccinated against a flavivirus, subsequent infection with another flavivirus (i.e., secondary flavivirus infection) can result in both a diminished IgM response and a rapid increase in neutralizing antibodies against multiple flaviviruses, which might preclude conclusive determination of which virus was responsible for the person's recent infection (4,50,(55)(56)(57)(58)(59).…”

Comprehensive response to Usutu virus following first isolation in blood donors in the Friuli Venezia Giulia region of Italy: Development of recombinant NS1-based serology and sensitivity to antiviral drugs

“…The Eurimmune USUV IgG ELISA is based on the viral structural proteins and these assays suffer from broad antigenic cross-reactivity of anti-flavivirus antibodies [32]. To this end the use of secreted flavivirus NS1 as an antigen alternative to virion proteins for the detection of IgM/G has proven to provide a better level of specificity [24,[33][34][35][36][37][38]. NS1 is secreted as a glycosylated oligomer in high amounts during the viremic phase and its detection is considered a marker of infection [39].…”