Mice with diverse microbial exposure histories as a model for preclinical vaccine testing

Caught in a trap: How pre-clinical studies in laboratory mice exaggerate vaccine responses

“…Indeed, the extensive history of exposure to influenza viruses in humans is a major confounding factor when translating pre-clinical studies into humans. Nonetheless, the findings described by Fiege and colleagues 1 are intriguing. Further characterization of the precise differences between SPF and dirty mice, namely, potential defects in germinal center (GC) formation/function that result in impaired Ab responses in dirty mice or alternative pathways relevant to protection from influenza virus, are warranted.…”

“…Recently, consideration has been given to the role of environmental factors in modulating host immune outcomes following infection and/or immunization, including diet/nutritional status, 2 , 3 microbiome, 4 baseline inflammatory state, 5 , 6 as well as the impact of co-infection or prior pathogen exposure, on innate or adaptive immunity. 1 , 7 …”

“… 8 , 9 To stimulate a pathogen-exposed basal state in mice, Fiege et al. 1 co-housed SPF mice with pet-store mice to facilitate their exposure to diverse microbes ( Figure 1 A). Increased frequencies of activated CD8 + T cells were observed in co-housed “dirty” mice.…”

“… Summary In a recent issue of Cell Host and Microbe , Fiege and colleagues 1 report that laboratory mice exposed to pathogens from pet-store mice exhibit impaired humoral immunity to influenza vaccination and display gene expression signatures that more authentically reflect human vaccine responses. …”

Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing

“…Mice which live in the wild were found to mirror the human immune system much more closely than lab-bred strains of mice [26]. Lab-bred mice co-housed with wild mice were found to have transcriptional signatures similar to humans when challenged with influenza vaccination, compared to lab-bred mice [27]. This suggests SPF-housed in-bred strains of mice used in research may not be beneficial for effectively representing the 'dirty' way in which humans live, undergoing constant challenge to the immune system.…”