Endy Timothy P, Nisalak Ananda, Chunsuttitwat Supamit, Vaughn David W, Green Sharone, Ennis Francis A, Rothman Alan L, Libraty Daniel H
Division of Virology, United States Army Medical Research Institute of Infectious Diseases, United States Army Medical Research and Materiel Command, Ft. Detrick, Maryland, USA.
J Infect Dis. 2004 Mar 15;189(6):990-1000. doi: 10.1086/382280. Epub 2004 Mar 1.
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.
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.
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.
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.
感染4种登革病毒（DV）中的任何一种都可能引发多种疾病，从轻度发热性疾病到典型登革热（DF），再到登革出血热（DHF），后者是一种可能危及生命的疾病。大多数登革出血热病例发生在相继的异型登革病毒感染之后。既往体液免疫在改变登革热疾病严重程度中的作用尚不清楚。
我们在登革热疾病高度流行的地区对儿童进行了一项前瞻性队列研究，研究既往中和抗登革病毒抗体（Abs）在改变继发登革3型病毒（D3V）、登革2型病毒（D2V）和登革1型病毒（D1V）感染中的作用。
在继发D3V感染中，针对D3V（参考病毒株和患者病毒分离株）的既往中和抗体水平较高与较低的病毒血症水平及较轻的疾病相关。针对D2V的既往中和抗体水平与继发D2V感染的严重程度无关。针对感染病毒分离株的既往中和抗体水平与继发D2V或D感染中的病毒血症水平无关。
交叉反应性记忆体液免疫反应似乎对有症状的继发D3V感染有益，但对继发D2V或D1V感染无益。这些结果可能对减毒活四价登革热疫苗的研发具有重要意义。
