Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.
Sci Transl Med
; 14(651): eabm3151, 2022 06 29.
Article
in En
| MEDLINE
| ID: mdl-35767652
ABSTRACT
Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua. Children protected from symptomatic infections had more anti-envelope (E) and anti-nonstructural protein 1 (NS1) total immunoglobulin G (IgG), IgG4, and greater Fc effector functions than those with symptoms. Fc effector functions were also associated with protection from hemorrhagic manifestations in the pre-symptomatic group. Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dengue
/
Dengue Virus
/
Coinfection
Type of study:
Diagnostic_studies
Limits:
Child
/
Humans
Language:
En
Journal:
Sci Transl Med
Journal subject:
CIENCIA
/
MEDICINA
Year:
2022
Document type:
Article
Affiliation country:
United States