Eliciting memory humoral responses with multiple vaccines in PBMC humanized mice 9254

Abstract Description Peripheral Blood Mononuclear Cell (PBMC) humanized mice (hPBMC mice), generated by injecting human PBMCs into immunodeficient mice, are increasingly used to study human immune responses particularly in cancer, infectious diseases, and immunotherapy research. These models are notable for their rapid engraftment of human cells and robust functional T-cell responses and for the ability to evaluate donor-specific responses in vivo. Despite its success in studying toxicity of preclinical Immunotherapeutics the model was believed to have certain limitations, including incomplete reconstitution of the human immune system, insufficient human cytokine support, and development of graft-versus-host disease (GvHD). Here, we demonstrate that hPBMC mice could elicit humoral responses against various antigens. We engrafted human PBMC into newly developed strains based on the NSG-MHC I/II DKO (#025216) from JAX and vaccinated the mice with standard vaccines (Tdap or COVID-19 mRNA) or with a recombinant spike protein from SARS-CoV-2 with or without adjuvant. Circulating tetanus toxoid, diptheria or SARS-CoV-2 spike specific human IgG were found elevated in vaccinated animals compared to PBS controls. Furthermore, these mice had increased numbers of total CD19+ B cells, activated B cells (CD38+) and CD138+ human plasma cells. These results highlight the potential of using hPBMC mice for research studying humoral immune responses. Topic Categories Vaccines and Immunotherapy (VAC)