Background The COVID-19 pandemic continues to be a worldwide threat and effective antiviral drugs and vaccines are being developed in a joint global effort. However, some elderly and immune-compromised populations are unable to raise an effective immune response against traditional vaccines. Aims We hypothesised that passive immunity engineered by the in vivo expression of anti-SARS-CoV-2 monoclonal antibodies (mAbs), an approach termed vectored-immunoprophylaxis (VIP), could offer sustained protection against COVID-19 in all populations irrespective of their immune status or age. Methods We developed three key reagents to evaluate VIP for SARS-CoV-2: (i) we engineered standard laboratory mice to express human ACE2 via rAAV9 in vivo gene transfer, to allow in vivo assessment of SARS-CoV-2 infection, (ii) to simplify in vivo challenge studies, we generated SARS-CoV-2 Spike protein pseudotyped lentiviral vectors as a simple mimic of authentic SARS-CoV-2 that could be used under standard laboratory containment conditions and (iii) we developed in vivo gene transfer vectors to express anti-SARS-CoV-2 mAbs. Conclusions A single intranasal dose of rAAV9 or rSIV.F/HN vectors expressing anti-SARS-CoV-2 mAbs significantly reduced SARS-CoV-2 mimic infection in the lower respiratory tract of hACE2-expressing mice. If translated, the VIP approach could potentially offer a highly effective, long-term protection against COVID-19 for highly vulnerable populations; especially immune-deficient/senescent individuals, who fail to respond to conventional SARS-CoV-2 vaccines. The in vivo expression of multiple anti-SARS-CoV-2 mAbs could enhance protection and prevent rapid mutational escape.
【저자키워드】 COVID-19, viral infection, respiratory infection, 【초록키워드】 SARS-CoV-2, Vaccine, immune response, Vaccines, spike, SARS-COV-2 infection, COVID-19 pandemic, monoclonal antibody, Infection, passive immunity, SARS-CoV-2 vaccines, anti-SARS-CoV-2, Population, antiviral drug, Laboratory, human ACE2, Protein, mice, vector, age, in vivo, expression, intranasal, mAbs, mAb, Immune status, Lentiviral vector, dose, Lower respiratory tract, effort, transfer, Express, reagent, offer, pseudotyped, approach, Prevent, effective, ENhance, joint, raise, evaluate, significantly, reduced, condition, individuals, expressing, translated, respond, sustained, hypothesised, VIP, 【제목키워드】 antibody, SARS-COV-2 infection, transfer,