Single-dose AAV-based vaccine induces a high level of neutralizing antibodies and provides long-term protection against SARS-CoV-2 in rhesus macaques

Coronavirus disease 2019 (COVID-19), which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, continues to threaten global public health. Developing a vaccine that only requires single immunization but provides long-term protection for the prevention and control of COVID-19 is important. Here, we developed an adeno-associated virus (AAV)-based vaccine expressing a stable receptor-binding domain (SRBD) protein. The vaccine requires only single shot, but provides effective neutralizing antibodies (NAbs) over 300 days in rhesus macaques (Macaca mulatta). In addition, the NAbs are at much higher levels than seen in the sera of convalescent patients. It is worth to note that though we detected the pre-existing AAV2/9 NAbs before immunization, the vaccine still induced high and effective NAbs, and did not boost the AAV2/9 NAbs levels in rhesus macaques. Importantly, AAV-SRBD immune sera efficiently neutralized the SARS-CoV-2 P.1/P.2, B.1.1.7, and B.1.351 variants. Together, all the data suggest the vaccine has great potential in preventing the spread of SARS-CoV-2.