Short-term repeated HRV-16 exposure results in an attenuated immune response in vivo in humans

Abstract

IntroductionNaturally, development of adaptive immunity following HRV infection affects the immune response. However, it is currently unclear whether or not HRV re-exposure within a short time frame leads to an altered innate immune response. The “experimental cold model” is used to investigate the pathogenesis of HRV infection and allows us to investigate the effects of repeated exposure on both local and systemic innate immunity.Methods40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. One week later, all subjects received HRV-16. Baseline seronegative subjects (n = 18) were included for further analysis.ResultsInfection rate was 82%. Primary HRV infection induced a marked increase in viral load and IP-10 levels in nasal wash, while a similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10 plasma levels, HRV infection did not induce systemic immune effects nor lower respiratory tract inflammation. With similar viral load present during the second HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually declined, with a similar trend for IL-10.ConclusionUpon a second HRV challenge one week after the first, a less pronounced response for several innate immune parameters is observed. This could be the result of immunological tolerance and possibly increases vulnerability towards secondary infections.

International consensus statement on allergy and rhinology: rhinosinusitis 2021

“…These studies suggest viral infection induced alteration of the immunologic homeostasis of the sinonasal mucosa, which could promote secondary bacterial infection. Interestingly, Koch et al also found repeated inoculation with RV 1 week after initial exposure had attenuated cytokine response 370 . This is consistent with anti‐inflammatory and immunosuppressive functions for IL‐10 seen in overexpression experiments by Stanic et al and could provide a mechanism for ABRS following RV infection 372 …”

“…Both studies found early increases in IL‐10 in controls exposed to RV. Koch et al also showed increases in IL‐6 and interferon gamma‐induced protein‐10 370 . These studies suggest viral infection induced alteration of the immunologic homeostasis of the sinonasal mucosa, which could promote secondary bacterial infection.…”

“…Koch et al and Heymann et al evaluated changes in inflammatory cytokine levels in healthy volunteers upon RV inoculation 370,371 . Both studies found early increases in IL‐10 in controls exposed to RV.…”

Human Rhinoviruses: a novel class of oncolytic virus

“…They are the major cause of the "common cold" via infection of the upper respiratory tract and are estimated to be responsible for up to half of all human infections [17]. Despite this impressive pathogenicity, in a study of short-term repeated HRV exposure, most (82%), but not all, human subjects infected with high titers of HRV caught colds, even when exposed directly through the upper respiratory tract [18]. Symptoms from infection tend to be mild and HRVs are eventually cleared from the body, though it has proven incredibly challenging, if not impossible, to generate effective vaccines [19][20][21].…”

Effects of Dietary Supplementation with Carrot-Derived Rhamnogalacturonan-I (cRG-I) on Accelerated Protective Immune Responses and Quality of Life in Healthy Volunteers Challenged with Rhinovirus in a Randomized Trial

“…Local immune responses to RV16 infection include the release of interferons and other pro-inflammatory mediators such as CXCL-10 and CXCL-8 leading to infiltration of inflammatory cells. Besides local responses, there are systemic responses including increased levels of T-helper and T-regulatory cell type cytokines [ 14 ] as well as an increase in plasma levels of CXCL-10 [ 15 , 16 ] and production of antibodies. RV16 challenge studies have also been employed to test the efficacy of various therapeutics [ 17 ].…”