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

Rebecca M Koch,Gerben Ferwerda,Jelle Gerretsen,Marien I De Jonge,Sandra Ten Bruggencate,Matthijs Kox,Corné Van Den Kieboom,Johannes G Van Der Hoeven,Peter Pickkers

doi:10.1371/journal.pone.0191937

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.

Highlights

Development of adaptive immunity following Human rhinoviruses (HRVs) infection affects the immune response
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
We recently demonstrated that seropositivity for HRV is associated with a virtually nullified immune response upon HRV challenge [29]

Summary

Methods

40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. Baseline seronegative subjects (n = 18) were included for further analysis. This randomized, placebo-controlled study was part of a larger trial investigating effects of serostatus and gender on the HRV-induced immune response[29]. The authors confirm that all ongoing and related trials for this intervention are registered. As this was a pilot study, no power calculation was performed. After approval by the local medical ethics committee CMO Arnhem-Nijmegen (NL42503.091.12; CMO 2012/476), 40 healthy, non-smoking, male and female subjects (ratio 1:1), aged 18–35 years gave written informed consent to participate in the study. Subjects were not allowed to take (prescription) drugs throughout the study

Results

Discussion

Conclusion