Inducing memory humoral responses using multiple vaccines in PBMC humanized mice

Humanized mouse models, such as those generated by administering human peripheral blood mononuclear cells (PBMC) into immunodeficient mice, hold great potential for studying immunotherapies and the immunogenicity of biologics and vaccines. Humanized mice are known for their quick engraftment of human cells, strong functional T-cell responses and for their capacity to assess donor-specific responses in vivo. However, these models face several limitations, including partial reconstitution of the human immune system, inadequate human cytokine support, and development of graft-versus-host disease (GvHD). To help address these issues we have developed new immunodeficient mouse strains and here show the potential of hPBMC mice to elicit humoral responses against various antigens. We engrafted human PBMC into NSG-SGM3xIL-15xDKO strain (JAX# 037320) followed by vaccination with formulated vaccines (Tdap, COVID-19 mRNA, or H5N1) or with antigen with or without adjuvant. Elevated levels of human IgG specific for tetanus toxoid, diphtheria, SARS-CoV-2 spike, or H5N1 were found in vaccinated animals compared to unvaccinated controls. Moreover, we also see an increase in total numbers of CD19+ B cells, activated B cells (CD38+) and CD138+ human plasma cells. These findings demonstrate that PBMC humanized mice provide a promising platform for evaluating humoral immunity.