Cellular and Humoral Immunity following Snow Mountain Virus Challenge

Lindesmith, Lisa C.; Moe, Christine L.; LePendu, Jacques; Frelinger, Jeffrey A.; Treanor, John J.; Baric, Ralph S.

doi:10.1128/jvi.79.5.2900-2909.2005

Cited by 236 publications

(289 citation statements)

References 51 publications

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“…Although previous studies have documented the immune responses to NoV challenge in infected individuals compared to uninfected individuals [12,18], this is the first study to our knowledge that compares the responses of Fig. 1.…”

Section: Discussionmentioning

confidence: 91%

Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding

Newman

Moe

Kirby

et al. 2016

Clinical and Experimental Immunology

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Summary Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription–polymerase chain reaction (RT–qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P < 0·01). Daily viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P < 0·05). Symptoms were not associated significantly with daily viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection.

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Section: Discussionmentioning

confidence: 91%

Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding

Newman

Moe

Kirby

et al. 2016

Clinical and Experimental Immunology

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“…The latter is in agreement with observations detected in humans. 96 Moreover, this study showed an inverse correlation between the expansion of T cells regardless of the subset and protection post challenge with NoV infection. P particles and VLPs induced similar protection rates as vaccine candidates with higher numbers of activated CD4 C T cells in different tissues, CD8 C T cells in the duodenum, T regs in peripheral blood and CD4 C CD25 ¡ FoxP3 C T regs producing TGF-b in the spleen following vaccination with the former.…”

Section: Animal Studiesmentioning

confidence: 94%

“…VLPs of 3 NoV strains (GI.1, GII.1, and GII.2) were used to stimulate PBMCs in vitro pre-and post-challenge of these volunteers with SMV in an attempt to determine the ability of SMV challenge to stimulate T cell responses. 96 While this study does not address protective immunity, it highlighted the possible impact of previous NoV infection whereby PBMCs from many infected and uninfected participants mounted an in vitro IFNg response and produced other cytokines including TNF-a and IL-2.…”

Section: Human Trialsmentioning

confidence: 99%

“…The role of CD4 C Th1 T cell responses against NoVs has been previously addressed. 96,104 The same group previously demonstrated that multivalent vaccination could be used as a tool to generate cross-reactive antibody immune responses to heterologous strains of NoV. 105 Decreased viral load following MNV challenge correlated with reduction in clinical disease but not protection.…”

Section: Animal Studiesmentioning

confidence: 99%

“…80,104,[123][124][125] Moreover, the intramuscular administration of candidate vaccines containing GI and GII strains stimulated strong immune responses against the vaccine genotype. 129,130 Human challenge studies 77,96 as well as vaccine studies (Table 2) tested the ability of different vaccine formulas to generate cross-reactive immune responses to account for the diversity of the circulating HuNoV strains. While the majority of these studies recruited healthy adults, HuNoV mainly affects children with acute gastroenteritis requiring hospitalizations.…”

Section: Human Trialsmentioning

confidence: 99%

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Norovirus vaccines: Correlates of protection, challenges and limitations

Melhem

2016

Human Vaccines & Immunotherapeutics

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Norovirus (NoV) is responsible for at least 50% of all gastroenteritis outbreaks worldwide. NoVs are classified into 6 different genogroups (GGI-GGVI) based on the viral capsid protein with NoV genogroup II genotype 4 (GII.4) being the predominant strain causing human diseases. Supportive therapy involving reversal of dehydration and electrolyte deficiency is the main treatment of NoV gastroenteritis. However, the worldwide increased recognition of NoV as an important agent of diarrheal gastroenteritis prompted researchers to focus on establishing preventive strategies conferring long-lasting immunity. This review describes the current status of animal and human vaccine models/studies targeting NoV and addresses the factors hampering the development of a broadly effective vaccine.

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