MHV68 is responsible for immune maturation in sequentially infected mice 4791

Abstract Description Up to 80% of therapies found effective in mice are not effective in humans due to factors such as differences in immune maturation, microbiota diversity, and genetic expression. Because of this, there have been many efforts to create a mouse model that best recapitulates the immune maturation of humans to better represent them in pre-clinical trials. Our model includes early exposure to six different viruses, Murine Rotavirus, Murine Gammaherpesvirus, Murine Norovirus, Flu, Murine Astrovirus, and Coxsackievirus chosen for their prevalence in human early life exposure. We show that early-life viral exposure in mice create and immunophenotype that recapitulates the immunophenotype of mature humans. This includes an expansion in both Myeloid and Lymphoid immune cells, increased effector function, an altered microbial flora in the gut, and expansion in T memory cells that persists into late adulthood. To show that this phenotype best models human immune maturation, we showed that these mice had blunted antibody responses to SARS-CoV-2 vaccination, also seen in humans, compared to robust antibody responses in mock mice. To determine which of these six viruses are essential for this phenotype, we establish that Murine Gammaherpesvirus, or MHV68, was enough to replicate almost all the results seen in the sequentially infected mice. We hope to improve this mouse model to be used as a more effective model of the human immune system in the context of therapy and vaccine development. Funding Sources Supported by NIH grants R01 OD024917, R01 AI139314, R01 AI141716, R01 AI173360, R21 AI176290, and R21 AI171831,R01 AI157155, T32 AI007163, T32 AI007163, T32 AI106688, T32 DK077653 and Ann W. & Spencer T. Olin-Chancellor’s Fellowship. Topic Categories Viral Immunology (VIR)