AUTHOR=Bonaiti Elena , Muraro Manuele G. , Robert Philippe A. , Jakscha Jens , Dirnhofer Stefan , Martin Ivan , Berger Christoph T. 

TITLE=Tonsil explants as a human in vitro model to study vaccine responses

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1425455

DOI=10.3389/fimmu.2024.1425455

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Vaccination is one of the most effective infection prevention strategies. Viruses with high mutation rates -such as influenza- escape vaccine-induced immunity and represent significant challenges to vaccine design. Influenza vaccine strain selection is based on circulating strains and immunogenicity testing in animal models with limited predictive outcomes for vaccine effectiveness in humans.</p></sec><sec><title>Methods</title><p>We developed a human <italic>in vitro</italic> vaccination model using human tonsil tissue explants cultured in 3D perfusion bioreactors to be utilized as a platform to test and improve vaccines.</p></sec><sec><title>Results</title><p>Tonsils cultured in bioreactors showed higher viability, metabolic activity, and more robust immune responses than those in static cultures. The <italic>in vitro</italic> vaccination system responded to various premanufactured vaccines, protein antigens, and antigen combinations. In particular, a multivalent <italic>in vitro</italic> immunization with three phylogenetically distant H3N2 influenza strains showed evidence for broader B cell activation and induced higher antibody cross-reactivity than combinations with more related strains. Moreover, we demonstrate the capacity of our <italic>in vitro</italic> model to generate de novo humoral immune responses to a model antigen.</p></sec><sec><title>Discussion</title><p>Perfusion-cultured tonsil tissue may be a valuable human <italic>in vitro</italic> model for immunology research with potential application in vaccine candidate selection.</p></sec>