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

• DOI: 10.1021/acsinfecdis.2c00296
• Publication Date: 2022-08-31T12:00:33Z
• Authors: Ya-Qian Li; Cheng Yan; Xi-Feng Wang; Mao-Ying Xian; Guo-Qing Zou; Xiao-Fei Gao; Rui Luo; Zheng Liu
• Keywords: 0301 basic medicine; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Antibodies, Neutralizing; 3. Good health; 03 medical and health sciences; Adjuvants, Immunologic; Vaccines, Subunit; Cytokines; Humans; Natural Killer T-Cells; Interleukin-4

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, αGC glycolipid (α-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 αGC-CPOEt elicited a strong cytokine response with increased IL-4 production. Remarkably, after three immunizations, SARS-CoV-2 RBD-Fc adjuvanted by αGC-CPOEt evoked robust neutralizing antibody responses that were about 5.5-fold more than those induced by αGC/RBD-Fc and 25-fold greater than those induced by unadjuvanted RBD-Fc. These findings imply that αGC-CPOEt could be investigated further as a new COVID-19 vaccine adjuvant to prevent current and future infectious disease outbreaks.