Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

Vaccines are the most efficient and effective means to prevent infectious diseases, but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development. 1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses. 1 Strategies to overcome this warrant is using adjuvants that amplify the immune response, and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection. 2 , 3 , 4 Although existing adjuvants have achieved promising results, research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019 (COVID-19). The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigen-presenting cell (APCs) uptake, achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses. 5 Previously, we reported a manganese nanoadjuvant (MnARK) and receptor-binding domain (RBD) monomer antigen formulated nanovaccine. 6 MnARK transported antigens to lymph nodes, activated the STING pathway, elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 6 Regarding the long-term protection potential of MnARK for subunit vaccine development, we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen, which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant (alum). 7 , 8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved (Supplementary Fig. 1a ). The size and zeta potential of MnARK-RBD dimer nanovaccine was ~58 nm and -14 mV, respectively (Supplementary Fig. 1b, c ).