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However, it has limitations, as most allergens are poorly immunogenic, resulting in an AIT process that can take years. Therefore, adjuvant selection becomes critical to achieve a more efficacious therapy. Our group has developed and tested an amphiphilic TLR7\/8 agonist (IMDQ) and a RIG-I agonist (SDI) that used alone, or in combination, have demonstrated strong adjuvant activity for influenza and SARS-CoV-2 vaccines in preclinical models. Here we describe the effect of these adjuvants in the sensitization of preclinical models with the ovalbumin (OVA) asthmatic allergic model via an in-depth humoral and cellular immune profiling. We assess their immune skewing and tolerance inducing capacities in previously sensitized preclinical models with different genetic backgrounds (C57BL\/6\n                  <jats:italic>vs.<\/jats:italic>\n                  BALB\/c mice). Moreover, we evaluate their effect in an unrelated antigenic challenge with influenza. Finally, we investigate the role of IgG subclasses and T-cell subpopulations in the protection against OVA challenge conferred by the combination of IMDQ and SDI. We demonstrate that OVA-immunization in combination with IMDQ+SDI prevents allergic sensitization via the induction of a balanced Type 1\/Type 2 response. Furthermore, it can revert the allergic phenotype in mice previously sensitized with OVA-Alum, through reducing lung eosinophilia, as well as IL-4 and IL-5 production. However, this was dependent on genetic background. IMDQ+SDI sensitization also led to reduced morbidity of a secondary influenza challenge in OVA-sensitized mice. Finally, we demonstrated that IgG2c, by itself, cannot protect from allergic sensitization and that both CD4\n                  <jats:sup>+<\/jats:sup>\n                  and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T-cells are needed for IMDQ+SDI prevention of eosinophil recruitment and activation upon intranasal OVA-challenge.\n                <\/jats:p>","DOI":"10.1101\/2025.06.23.659362","type":"posted-content","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T11:30:10Z","timestamp":1750937410000},"source":"Crossref","is-referenced-by-count":0,"title":["A combination TLR7\/8 and RIG-I agonist adjuvant reverts asthmatic allergic sensitization and prevents aggravated influenza infection in OVA-sensitized mice"],"prefix":"10.64898","author":[{"given":"Juan Garc\u00eda-Bernalt","family":"Diego","sequence":"first","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of 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