Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration

Abstract

While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs.

Omicron COVID-19 Immune Correlates Analysis of a Third Dose of mRNA-1273 in the COVE Trial

“…We previously applied multiple statistical frameworks to assess several immune markers including serum IgG binding antibodies (bAbs) against Spike and neutralizing antibodies (nAbs), measured on D57, as correlates of risk (CoRs) and correlates of protection (CoPs) against COVID-19 through ~4 months post dose 2 ( 3, 4 ). Using antibody decay models we also demonstrated that the nAb titer at the time of exposure correlated with COVID-19 ( 5 ). In all these analyses, the markers were measured against Ancestral Spike: bAbs against index (vaccine-insert) Spike and nAbs against index Spike with the D614G mutation (for simplicity, we refer hereafter to both of these as “Ancestral”).…”

“…In SARS-CoV-2 naives, receipt of a third dose was estimated to provide a 46% (95% CI: 20%, 64%) relative reduction in Omicron COVID-19 throughout follow-up compared to an unboosted (two-dose recipient) control group. Using these unboosted participants as a dynamic control group, we analyzed time-varying predicted antibody levels where the instantaneous risk of Omicron COVID-19 on any given day depends on the predicted antibody level on that day using a Cox model with calendar time index [see Methods and ( 5 )]. Model-predicted values on the day of disease onset correlated well with the actual antibody readouts on the day of disease onset ( Figures S29, S30 ).…”

The magnitude and cross reactivity of SARS-CoV-2 specific antibody responses in vaccinated and unvaccinated Sri Lankan children and association with nutrition status

“…Although the seropositivity rates among different age groups did not differ, there were significant differences in ACE2 blocking antibody levels, which are surrogate markers of Nabs [18,21]. Nabs antibodies prevent binding to the ACE2 receptor and have shown to associate with protection [29]. Children with undernutrition (<3 rd BMI centile for age), had significantly lower ACE2 blocking antibody titres compared to children of healthy weight.…”

Early antiviral CD4 and CD8 T cell responses and antibodies are associated with upper respiratory tract clearance of SARS-CoV-2

“…Our study has limitations. It is intrinsically challenging to disentangle the roles of T cells from the roles of antibodies in combatting SARS-CoV-2 in humans 17,19,20 . The study was also underpowered to distinguish whether the CD4 and CD8 T cell responses were each independently associated with lower viral loads.…”