Key clinical point: Among nonsecretors – individuals who express fewer fucosylated histoblood group antigen carbohydrates and consequently are less susceptible to some norovirus strains – natural infection with norovirus strain GII.2 induced durable cellular and antibody immunity.
Major finding: Immunity lasted for at least 30 days for T cells, monocytes, and dendritic cells and at least 180 days for blocking antibodies.
Study details: Flow cytometry and neutralizing antibody assays of blood specimens from four related nonsecretor adults who were infected with norovirus strain GII.2 during an outbreak.
Disclosures: The National Institutes of Health, the Wellcome Trust, the Centers for Disease Control and Prevention, and a Cancer Center Core support provided funding. Ms. Lindesmith and her associates reported having no relevant conflicts of interest.
Lindesmith LC et al. Cell Molec Gastroenterol Hepatol. 2020;10:245-67.
Noroviruses belonging to genogroup II.4 are the leading cause of acute gastroenteritis, but our understanding of norovirus immunity remains incomplete. Most studies have focused on humoral responses and have shown that antibodies may be short lived, strain specific, and not always protective against rechallenge. On the other hand, human innate and T-cell immunity have received little attention despite evidence from the mouse norovirus model that they are critical for limiting viral spread and clearing antigen.
In this study, Lindesmith et al. conducted broad phenotypic and functional analysis of innate and adaptive immune responses following infection with a GII.2 strain of norovirus. Their cohort consists of “nonsecretors,” subjects who express a limited repertoire of histoblood group antigens and are therefore naturally resistant to GII.4 infection. Since nonsecretors have no pre-existing immunity against GII.4 viruses, this system enables the authors to test cross-reactivity of GII.2-specific T cells against GII.4 virus-like particles (VLPs).
The authors showed broad immune activation against natural norovirus infection. Following GII.2 infection, T-cell responses persist for at least a month and, importantly, are cross-reactive against GII.4 VLPs. These findings suggest that T cells may target conserved viral epitopes and play an important role in long-term protection against reinfection.
Developing an effective norovirus vaccine will require a detailed understanding of immune correlates of protection, and this study is a step in the right direction. In future work, tracking epitope-specific T cells must further define the phenotype, functionality, and localization of the norovirus T-cell repertoire.
Vesselin Tomov, MD, PhD, is assistant professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia. He has no conflicts of interest.