Monoclonal antibody levels and protection from COVID-19

Abstract

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in the in vivo concentration of monoclonal antibodies, and the associated protection from COVID-19, over time to model the dose-response relationship of monoclonal antibodies for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a monoclonal antibody concentration of 939-fold of the in vitro IC50 (95% CI: 135 - 2073). This relationship provides a quantitative tool allowing prediction of the prophylactic efficacy and duration of protection for new monoclonal antibodies administered at different doses and against different SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either monoclonal antibody treatment or vaccination. We find no evidence for a difference between the 50% protective titer for monoclonal antibodies and vaccination, although vaccination is predicted to be capable of achieving a higher maximum level of protection.

Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis

“…In addition, since T-cell help is required for the generation of high titre neutralising antibody responses, they likely play an important indirect role in protection. Therefore, while we can conclude that neutralising antibodies are associated with protection from severe disease (this study) and that passively administered antibodies can reduce severe diseases 42 , more work is still required to determine the contribution of cellular immune responses to protection.…”

“…Administration of antibodies during symptomatic SARS-CoV-2 infection can reduce the risk of subsequent hospitalisation or death by up to 85% 40 (reviewed in ref. 42 ). This demonstrates a direct role for antibodies in reducing infection severity, independent of their role in preventing the acquisition of infection.…”

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

“…Several studies of COVID-19 vaccines have established that a cellculture pseudovirus neutralizing titer of ~10 2 translates into human vaccine efficacy against symptomatic disease of ~90% [55][56][57][58][59] . In addition, clinical trials have established a correlation between anti-SARS-CoV-2 monoclonal antibody levels (i.e., humoral immunity alone) and protection from COVID-19 60,61 . Indeed, SARS-CoV-2 variant booster vaccines have been accepted by the FDA and EMA for emergency use authorization using neutralizing antibody titer as a correlate of protection 62,63 .…”

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

“…52-56 In addition, clinical trials have established a correlation between anti-SARS-CoV-2 monoclonal antibody levels (i.e., humoral immunity alone) and protection from COVID-19. 57,58 Indeed, SARS-CoV-2 variant booster vaccines have been accepted by the FDA and EMA for emergency use authorization using neutralizing antibody titer as a correlate of protection. 59,60…”