A New iNKT-Cell Agonist-Adjuvanted SARS-CoV-2 Subunit Vaccine Elicits Robust Responses

Adjuvants are essential components of vaccines. Invariant natural killer T (iNKT) cells are a distinct subset of T cells that function to bridge the innate and adaptive immunities and are capable of mediating strong and rapid responses to a range of diseases, including cancer and infectious disease. An increasing amount of evidence suggests that iNKT cells can help fight viral infection. In particular, iNKT-secreting IL-4 is a key mediator of humoral immunity and has a positive correlation with the levels of neutralizing antibodies. As iNKT cell agonists, alpha GC glycolipid (alpha- galactosylceramide, or KRN7000) and its analogues as vaccine adjuvants have begun to provide vaccinologists with a new toolset. Herein we found that a new iNKT-cell agonist alpha GC-CPOEt elicited a strong cytokine response with increased IL-4 production. Remarkably, after three immunizations, SARS-CoV-2 RBD-Fc adjuvanted by alpha GC-CPOEt evoked robust neutralizing antibody responses that were about 5.5-fold more than those induced by alpha GC/RBD-Fc and 25-fold greater than those induced by unadjuvanted RBD-Fc. These findings imply that alpha GC-CPOEt could be investigated further as a new COVID-19 vaccine adjuvant to prevent current and future infectious disease outbreaks.