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Heterotypic humoral and cellular immune responses following Norwalk virus infection.

ABSTRACT: 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.

SUBMITTER: Lindesmith LC

PROVIDER: S-EPMC2812379 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Heterotypic humoral and cellular immune responses following Norwalk virus infection.

Lindesmith Lisa C LC Donaldson Eric E Leon Juan J Moe Christine L CL Frelinger Jeffrey A JA Johnston Robert E RE Weber David J DJ Baric Ralph S RS

Journal of virology 20091209 4

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 recombina ...[more]

PMID: 20007270

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Project description:Understanding immune memory to COVID-19 vaccines is critical for the design and optimal vaccination schedule for curbing the COVID-19 pandemic. Here, we assessed the status of humoral and cellular immune responses at 1, 3, 6, and 12 months after two-dose CoronaVac vaccination. A total of 150 participants were enrolled, and 136 of them completed the study through the 12-month endpoint. Our results show that, at 1 month after vaccination, both binding and neutralizing antibodies could be detected; the seropositive rate of binding antibodies and seroconversion rate of neutralizing antibodies were 99% and 50%, respectively. From 3 to 12 months, the binding and neutralizing antibodies declined over time. At 12 months, the binding and neutralizing antibodies were still detectable and significantly higher than the baseline. Gamma interferon (IFN-γ) and interleukin 2 (IL-2) secretion specifically induced by the receptor-binding domain (RBD) persisted at high levels until 6 months and could be observed at 12 months, while the levels of IL-5 and granzyme B (GzmB) were hardly detected, demonstrating a Th1-biased response. In addition, specific CD4+ T central memory (TCM), CD4+ effector memory (TEM), CD8+ TEM, and CD8+ terminal effector (TE) cells were all detectable and functional up to 12 months after the second dose, as the cells produced IFN-γ, IL-2, and GzmB in response to stimulation of SARS-CoV-2 RBD. Our work provides evidence that CoronaVac induced not only detectable binding and neutralizing antibody responses, but also functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells for up to 12 months. IMPORTANCE CoronaVac is an inactivated vaccine containing whole-virion SARS-CoV-2, which has been approved in 43 countries for emergency use as of 26 November 2021. However, the long-term immune persistence of the CoronaVac vaccine is still unknown. Here, we reported the status of the persistence of antibodies and cellular responses within 12 months after two doses of CoronaVac. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

Dataset Information

Heterotypic humoral and cellular immune responses following Norwalk virus infection.

Publications

Heterotypic humoral and cellular immune responses following Norwalk virus infection.

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