RBD-based SARS-CoV-2 vaccine adjuvanted with cyclic di-adenosine monophosphate enhances humoral and cellular immunity in mice

GERMANÓ, MARÍA JOSÉ; CONSTANZA GIAI; CARGNELUTTI, DIEGO ESTEBAN; MARIA ISABEL COLOMBO; SEBASTIÁN BLANCO; BRENDA KONIGHEIM; LORENA SPINSANTI; JAVIER AGUILAR; SANDRA GALLEGO; VALDEZ, HUGO ALBERTO; MACKERN-OBERTI, JUAN PABLO; SANCHEZ SANCHEZ, MARIA VICTORIA

Atlanta

Congreso; Keystone Symposia Vaccinology During and After COVID-19 (F6); 2023

Keystone Symposia

Novel adjuvants are highly desired to enhance the immune responses of SARS-CoV-2 vaccines.This study explores the potential of using the stimulator of interferon genes (STING) agonistadjuvant, cyclic di-adenosine monophosphate (c-di-AMP), in a SARS-CoV-2 vaccine based on thereceptor binding domain (RBD). Mice were immunized with two doses of monomeric RBDadjuvanted with c-di-AMP via intramuscular administration, and their immune responses werecompared to those of mice vaccinated with RBD adjuvanted with aluminium hydroxide (Al(OH)3)or without any adjuvant.The results demonstrated that mice vaccinated with RBD+c-di-AMP exhibited significantlystronger immune responses than those vaccinated with RBD+Al(OH)3 or RBD alone (n.d.).Following two immunizations, the RBD+c-di-AMP group showed consistent enhancements in themagnitude of RBD-specific IgG antibody response compared to the RBD+Al(OH)3 and RBD alonegroups. Furthermore, analysis of IgG subtypes indicated a predominantly Th1-biased immuneresponse, with predominant IgG2c secretion, in mice vaccinated with RBD+c-di-AMP, whereas aTh2-biased response was observed in those vaccinated with RBD+Al(OH)3. Remarkably, even inaged mice, c-di-AMP improved RBD-immunogenicity after three doses.Additionally, the RBD+c-di-AMP vaccine demonstrated superior neutralizing antibody responsesas determined by pseudovirus neutralization assay, and by plaque reduction neutralizationassay with SARS-CoV-2 Wild Type B.1. Moreover, the RBD+c-di-AMP vaccine promoted IFN-γsecretion in spleen cell cultures after RBD stimulation.In conclusion, these findings suggest that c-di-AMP significantly enhances RBD-specific immuneresponses, making it a promising adjuvant option for future COVID-19 vaccines.