Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand.
BACKGROUND
Infection with any 1 of the 4 dengue viruses (DVs) can produce several illnesses, ranging from a mild febrile illness to classic dengue fever (DF) to dengue hemorrhagic fever (DHF), a potentially life-threatening disease. Most DHF cases occur after sequential heterotypic DV infections. The role of preexisting humoral immunity in modifying severity of dengue disease is not well understood.


METHODS
We conducted a prospective cohort study of children in a region where dengue disease is hyperendemic and examined the role of preexisting neutralizing anti-DV antibodies (Abs) in modifying secondary dengue-3 virus (D3V), dengue-2 virus (D2V), and dengue-1 virus (D1V) infections.


RESULTS
In secondary D3V infection, higher levels of preexisting neutralizing Ab directed against D3V (reference virus strain and patient's virus isolate) were associated with lower viremia levels and milder disease. Preexisting neutralizing Ab levels against D2V were not associated with severity of secondary D2V infection. The levels of preexisting neutralizing Ab against the infecting virus isolates were not associated with viremia levels in secondary D2V or D1V infections.


CONCLUSIONS
Cross-reactive memory humoral immune responses appear to be beneficial in symptomatic secondary D3V infection, but not in secondary D2V or D1V infection. These results may have important implications for the development of live attenuated tetravalent dengue vaccines.
Endy
Timothy P
TP
Division of Virology, United States Army Medical Research Institute of Infectious Diseases, United States Army Medical Research and Materiel Command, Ft. Detrick, Maryland, USA.
Nisalak
Ananda
A
Chunsuttitwat
Supamit
S
Vaughn
David W
DW
Green
Sharone
S
Ennis
Francis A
FA
Rothman
Alan L
AL
Libraty
Daniel H
DH
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D011446:Prospective Studies; D012703:Serotyping; D014766:Viremia / Q000276:immunology*
D000914:Antibodies, Viral