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. 2015 Aug 1;212(3):397-405.
doi: 10.1093/infdis/jiv053. Epub 2015 Jan 29.

Mucosal and Cellular Immune Responses to Norwalk Virus

Sasirekha Ramani  1 , Frederick H Neill  1 , Antone R Opekun  2 , Mark A Gilger  3 , David Y Graham  4 , Mary K Estes  4 , Robert L Atmar  4
Affiliations

Mucosal and Cellular Immune Responses to Norwalk Virus

Sasirekha Ramani et al. J Infect Dis. .

Abstract

Background: Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses having focused on serological responses to infection.

Methods: We used saliva, feces, and peripheral blood mononuclear cells collected from persons who were administered Norwalk virus (NV) to characterize mucosal (salivary and fecal immunoglobulin A [IgA]) and cellular (NV-specific IgA and immunoglobulin G [IgG] antibody-secreting cells and total and NV-specific IgA and IgG memory B cells) immune responses following infection.

Results: Prechallenge levels of NV-specific salivary IgA and NV-specific memory IgG cells correlated with protection from gastroenteritis, whereas prechallenge levels of NV-specific fecal IgA correlated with a reduced viral load. Antibody-secreting cell responses were biased toward IgA, while memory B-cell responses were biased toward IgG. NV-specific memory B cells but not antibody-secreting cells persisted 180 days after infection.

Conclusions: NV-specific salivary IgA and NV-specific memory IgG cells were identified as new correlates of protection against NV gastroenteritis. Understanding the relative importance of mucosal, cellular, and humoral immunity is important in developing vaccine strategies for norovirus disease prevention.

Keywords: IgA; IgG; Norovirus; Norwalk virus; antibody-secreting cells; correlate of protection; fecal IgA; immune response; memory B cells; salivary IgA.

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Figures

Figure 1.
Figure 1.
Salivary and fecal immunoglobulin A (IgA) responses to Norwalk virus (NV) infection. A significant difference in preexisting IgA levels between infected subjects with and those without gastroenteritis was seen with NV-specific salivary (A) but not fecal (B) IgA. Among the infected subjects, the preexisting histo-blood group antigen (HBGA) blocking antibody (BT50) in serum correlates with salivary (C) but not fecal (D) IgA.
Figure 2.
Figure 2.
Kinetics of cellular immune response in Norwalk virus (NV) infection. Geometric mean number of NV-specific antibody-secreting cells (ASCs; A) and memory B cells (B) were plotted for each time point. Error bars represent the standard error of mean. Abbreviations: IgA, immunoglobulin A; IgG, immunoglobulin G; PBMC, peripheral blood mononuclear cell.
Figure 3.
Figure 3.
Correlation of day 14 Norwalk virus–specific immunoglobulin A (IgA) antibody-secreting cell (ASC) levels with peak viral load in 20 infected persons. Abbreviation: PBMC, peripheral blood mononuclear cell.
Figure 4.
Figure 4.
Comparison of prechallenge memory B cells levels among Norwalk virus (NV)-infected persons with and those without gastroenteritis. There were significant differences in preexisting NV-specific immunoglobulin G (IgG) memory B cells (A) but not NV-specific immunoglobulin A (IgA) memory B cells (B).
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References

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