Elderly Patients Humoral and Mucosal Immune Responses to Norovirus

In a prospective study of the immune response to norovirus in elderly patients, salivary immunoglobulin A (IgA) increased as early as 5 days after onset of symptoms and correlated strongly with serum IgA titers and blockade antibodies. These levels then remained elevated for at least 3 months, according to data published in the Journal of Infectious Diseases.

Noroviruses are the most common cause of epidemic and sporadic outbreaks of acute gastroenteritis among all age groups, globally. Preexisting norovirus-specific salivary IgA levels, circulating norovirus-specific IgG memory B cells, and the presence of antibodies targeting epitopes of histo-blood group antigens in serum have been linked to protection against disease in previous studies. Norovirus-specific salivary IgA levels correlate with serum IgA levels, which function to block the binding of norovirus virus-like particles to histo-blood group antigens.

The investigators, therefore, studied the mucosal and systemic immune response to norovirus at 43 long-term care facilities between November 2009 and January 2013, using baseline saliva samples collected at 14 facilities. They further collected saliva as well as acute and convalescent sera from case and control participants up to day 84 from 10 outbreaks.

In baseline saliva samples, norovirus-specific IgA levels were low and increased in symptomatic patients and asymptomatic viral shedders at day 5 after onset. Using receiver operating characteristics analysis, prior norovirus infections were accurately identified in 92% of participants. Seroconversion for IgG (80%), IgA (78%), and blockade antibodies (87%) was observed in case participants compared with asymptomatic shedders, who demonstrated an 18% seroconversion of IgG and 22% for each IgA and blockade antibodies. The data also showed that salivary IgA levels strongly correlated with increased convalescent serum IgA titers and blockade antibodies.

Results of this study may, however, lack generalizability to the general population, as it was conducted at a relatively small number of long-term care facilities with residents who are generally older and more medically frail. There was also no prescreening for norovirus antibodies, the presence of which may have an effect on the immune responses to new infections. In some cases, saliva sample collection did not begin at day 0, and in others, saliva was not provided at all. Furthermore, although serum samples during the acute stage were collected during the first week, they were not always collected on the same day post-onset in all cases. These samples were then only tested for antibodies, with the norovirus-like particles matching the genotype for each outbreak. Last, investigators noted that protein loss may have occurred even though individual variations in salivary IgA titers were corrected by normalizing to total salivary IgA.

The investigators described fluctuations in norovirus-specific salivary IgA titers throughout the course of an outbreak. This data showing elevated titers starting 8 days after infection may therefore serve as a screening method for vaccine response, especially in cases in which drawing blood is difficult or infeasible. The researchers believed that “[a] single salivary sample could be used to identify acute infection in a suspected outbreak or to monitor population salivary IgA.” They recommended, however, that further studies determine whether blockade antibodies are present in saliva, and whether they are produced locally in mucosal tissue or as part of the systemic response. With these data, it would be possible to elucidate potential correlates of protection, as these are critically needed for the assessment of future vaccine efficacy.

Reference

Costantini VP, Cooper EM, Hardaker HL, et al. Humoral and mucosal immune responses to human norovirus in the elderly [published online January 20 2020]. J Infect Dis. doi:10.1093/infdis/jiaa021