Tracking the polyclonal neutralizing antibody response to a dengue virus serotype 1 type-specific epitope across two populations in Asia and the Americas

Abstract

The four dengue virus serotypes (DENV1-4) cause major public health problems worldwide. Highly neutralizing type-specific human monoclonal antibodies (hmAbs) target conformation-dependent epitopes on the DENV envelope protein, including 1F4, a DENV1 type-specific hmAb. Using a recombinant DENV2 virus displaying the DENV1 1F4 epitope (rDENV2/1), we measured the proportion and kinetics of DENV1 neutralizing antibodies targeting the 1F4 epitope in individuals living in Asia and the Americas where different DENV1 genotypes were circulating. Samples from 20 individuals were analyzed 3 and 18 months post-primary DENV1 infection, alongside samples from 4 individuals collected annually for four years post-primary DENV1 infection, from two studies in Nicaragua. We also analyzed convalescent post-primary DENV1 plasma samples from Sri Lankan individuals. We found that neutralizing antibodies recognizing the 1F4 epitope vary in prevalence across both populations and were detected from 20 days to four years post-infection. Additionally, both populations displayed substantial variability, with a range of high to low proportions of DENV1 type-specific neutralizing antibodies recognizing the 1F4 epitope seen across individuals. Thus, the 1F4 epitope is a major but not exclusive target of type-specific neutralizing antibodies post-primary infection with different DENV1 genotypes in Asia and Latin America, and additional epitopes likely contribute to type-specific neutralization of DENV1.

Ehrlichia chaffeensis and E. canis hypothetical protein immunoanalysis reveals small secreted immunodominant proteins and conformation-dependent antibody epitopes

“…To our knowledge, such a large abundance of proteins with conformational epitopes has never been reported previously in other pathogens and indicates that the Ehrlichia immunomes have a predominance of epitopes with conformation-dependence. Conformational antibody epitopes have been experimentally identified in human pathogens, mostly reported in viruses, such as functional epitopes on hepatitis E virions/capsids, the orf virus major envelope protein B2L and dengue virus envelope E glycoprotein [43][44][45] . A few conformation-dependent epitopes have also been described in bacterial proteins, such as E. ch.…”

Antibody reactive immunomes of Ehrlichia chaffeensis and E. canis are diverse and defined by conformational antigenic determinants

“…The application of IVTT in antigen discovery is the key to identification of conformation-dependent immunoreactive proteins, because IVTT generally expresses soluble proteins in native conformation, although posttranslational modifications may not exist ( Shimizu et al., 2006 ; Carlson et al., 2012 ). The majority of bacterial B-cell epitopes are estimated to be conformational, and many pathogens are known to have immunoreactive proteins with conformational antibody epitopes ( Portnyagina et al., 2018 ; Andrade et al., 2019 ; Liu et al., 2019 ; He et al., 2020 ). However, prior to our studies, the defined E. chaffeensis and E. canis immunoreactive proteins were limited to those with only major linear epitopes due to the limitations in the approaches used for screening ( McBride and Walker, 2010 ; Lina et al., 2016 ).…”

Evolution of a Functionally Intact but Antigenically Distinct DENV Fusion Loop

“…Of note, EDE1-C10 neutralization potency was also reduced in our FLM variant, further indicating our mutations are affecting the tip of the EDII region which partially overlaps with the EDE1 epitope 25 . In combination with other chimeric DENVs, [26][27][28] D2-FLM provides a reagent to distinguish between type-specific, protective cross-reactive (e.g. envelopdimer-epitope), 29,30 and antibody-dependent enhancement-prone cross-reactive (e.g.…”