Heterotypic Humoral and Cellular Immune Responses following Norwalk Virus Infection

被引:103
作者
Lindesmith, Lisa C.
Donaldson, Eric [2 ]
Leon, Juan [3 ]
Moe, Christine L. [3 ]
Frelinger, Jeffrey A. [2 ]
Johnston, Robert E. [4 ]
Weber, David J. [5 ]
Baric, Ralph S. [1 ,2 ,4 ]
机构
[1] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[3] Emory Univ, Hubert Dept Global Hlth, Atlanta, GA 30322 USA
[4] Carolina Vaccine Inst, Chapel Hill, NC USA
[5] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
BLOOD GROUP ANTIGENS; REVERSE-TRANSCRIPTION-PCR; CAPSID PROTEIN FORMS; ACUTE GASTROENTERITIS; MONOCLONAL-ANTIBODIES; GENOGROUP-I; MOLECULAR CHARACTERIZATION; GENETIC DIVERSITY; HUMAN NOROVIRUS; SECRETOR FUT2;
D O I
10.1128/JVI.02179-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Norovirus immunity is poorly understood as the limited data available on protection after infection are often contradictory. In contrast to the more prominent GII noroviruses, GI norovirus infections are less frequent in outbreaks. The GI noroviruses display very complex patterns of heterotypic immune responses following infection, and many individuals are highly susceptible to reinfection. To study the immune responses and mechanisms of GI. 1 persistence, we built structural models and recombinant virus-like particles (VLPs) of five GI strains: GI. 1-1968, GI. 1-2001, GI. 2-1999, GI. 3-1999, and GI. 4-2000. Structural models of four GI genotype capsid P domain dimers suggested that intragenotype structural variation is limited, that the GI binding pocket is mostly preserved between genotypes, and that a conserved, surface-exposed epitope may allow for highly cross-reactive immune responses. GI VLPs bound to histo-blood group antigens (HBGAs) including fucose, Lewis, and A antigens. Volunteers infected with GI. 1-1968 (n = 10) had significant increases between prechallenge and convalescent reactive IgG for all five GI VLPs measured by enzyme immunoassay. Potential cross-neutralization of GI VLPs was demonstrated by convalescent-phase serum cross-blockade of GI VLP-HBGA interaction. Although group responses were significant for all GI VLPs, each individual volunteer demonstrated a unique VLP blockade pattern. Further, peripheral blood mononuclear cells (PBMCs) were stimulated with each of the VLPs, and secretion of gamma interferon (IFN-gamma) was measured. As seen with blockade responses, IFN-gamma secretion responses differed by individual. Sixty percent responded to at least one GI VLP, with only two volunteers responding to GI. 1 VLP. Importantly, four of five individuals with sufficient PBMCs for cross-reactivity studies responded more robustly to other GI VLPs. These data suggest that preexposure history and deceptive imprinting may complicate PBMC and B-cell immune responses in some GI. 1-1968-challenged individuals and highlight a potential complication in the design of efficacious norovirus vaccines.
引用
收藏
页码:1800 / 1815
页数:16
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