Antibody avidity following secondary dengue virus type 2 infection across a range of disease severity

Abstract

Background The four dengue virus serotypes (DENV1-4) are responsible for the most prevalent mosquito-borne viral illness in humans. DENV causes a spectrum of disease from self-limiting dengue fever (DF) to severe, life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Antibodies from one infection can contribute to either protection or increased disease severity in a subsequent infection with a distinct DENV serotype. The effectiveness of the antibody response is modulated by both the affinity and avidity of the antibody/antigen interaction. Objectives We investigated how antibody avidity developed over time following secondary DENV2 infection across different disease severities. Study design We analyzed sera from 42 secondary DENV2-infected subjects (DF, n=15; DHF, n=16; DSS, n=11) from a pediatric hospital-based dengue study in Nicaragua. IgG avidity against DENV2 virions was measured in samples collected during acute and convalescent phases as well as 3, 6, and 18 months post-illness using a urea enzyme-linked immunosorbent assay. Results The data show a significant increase in avidity from acute to convalescent phase followed by a decrease from convalescent phase to 3 months post-symptom onset, then a plateau. Linear regression analysis comparing antibody avidity between disease severity groups over time indicate that individuals with more severe disease (DHF/DSS) experienced greater decay in antibody avidity over time compared to less severe disease (DF), and ROC curve analysis showed that at 18 months post-illness, lower avidity was associated with previously having experienced more severe disease. Conclusions These data suggest that increased dengue disease severity is associated with lower antibody avidity at later time-points post-illness.

Seroprevalence of dengue IgG antibodies in symptomatic and asymptomatic individuals three years after an outbreak in Zhejiang Province, China

“…We can concluded that all infecting serotypes were DENV-3 related to the outbreak in 2009 and all symptomatic persons and asymptomatic individuals were all primary infection. According to previous reports [ 3 – 9 ], the existence of dengue antibodies could enhance dengue infection and Zika infection. Accordingly, we suggest that more attention should be paid to dengue or zika cases who have been infected with dengue viruses, even they contracted dengue viruses many years ago.…”

“…DENV cause a spectrum of diseases ranging from subclinical manifestations or a mild, self-limiting disease, dengue fever (DF), to a more severe disease, dengue hemorrhagic fever (DHF), which can progress to dengue shock syndrome (DSS) and death. Previous studies reported that cross-reacting antibodies enhanced dengue infection in humans and antibody dependent enhancement (ADE) had been proposed as the early mechanism underlying DHF/DSS [ 3 – 7 ]. Moreover, recent studies have reported that human antibody responses after dengue virus infection were highly cross-reactive with Zika virus and was able to drive ADE of Zika infection [ 8 , 9 ].…”

Immunogenicity of a novel tetravalent vaccine formulation with four recombinant lipidated dengue envelope protein domain IIIs in mice

“…It has been shown that antibody avidity correlates with a neutralizing capacity in natural infections of human by dengue virus 46 . Moreover, an increased severity of dengue diseases is associated with a lower antibody avidity at later time-points after infection 47 . Therefore, antibody avidity should be an important index to evaluate vaccine candidates.…”

Recent advances in understanding dengue

“…An increase in disease severity was observed when the interval between first and second infections was 20 years as opposed to 4 years 30 . As an explanation, it was observed that severe disease at a long interval was correlated with an observed steady decrease in heterotypic antibody titers over a long period 37, 38 . During secondary dengue infections, adults are at greater risk than children of bleeding whereas children are at greater risk than adults of vascular permeability 39 .…”