SARS-CoV-2 binding and neutralizing antibody levels after Ad26.COV2.S vaccination predict durable protection in rhesus macaques

Abstract

Several COVID-19 vaccines have recently gained authorization for emergency use. Limited knowledge on duration of immunity and efficacy of these vaccines is currently available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short-lived, and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection. In this work, we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike protein in rhesus macaques and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We show that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of Spike-binding and neutralizing antibodies, indicating that Ad26.COV2.S could confer durable protection in humans and immunological correlates of protection may enable the prediction of durability of protection.

Defining the determinants of protection against SARS-CoV-2 infection and viral control in a dose-down Ad26.CoV2.S vaccine study in nonhuman primates

“…As previously published in [ 29 ], vaccine doses as low as 2 × 10 9 VPs provided robust protection in the lower respiratory tract, whereas protection in the upper respiratory tract showed a negative dose dependency ( Fig 1B ), in which a higher dose (1.125 × 10 10 VPs) was required for protection. Additionally, as previously reported [ 30 ], higher doses generated consistently higher binding antibody titers and neutralizing titers, in addition to stimulating increased T-cell cytokine production above an observed threshold ( Fig 1B ) in response to both SARS-CoV-2 spike and receptor-binding domain (RBD). This illustrates the complete protection provided by high doses of the vaccine that wanes as a function of dose and highlights the need to deeply mine for correlates of protection in the upper respiratory tract.…”

Durability and expansion of neutralizing antibody breadth following Ad26.COV2.S vaccination of mice

“…Pseudotyped viruses expressing the SARS-CoV-2 S protein were used to assess antibody neutralization, rather than live SARS-CoV-2 viruses. Prior work has established the pseudovirus platform and demonstrated strong positive correlations between pseudovirus and live virus NAb titers 7 , 9 , 11 , 53 . Future preclinical or clinical studies could further explore the observations made in the present study by probing the mechanisms underpinning the broad neutralization of variants.…”

Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis

“…2 . Such copious amounts of literature for model building may not be available for all pathogens; however, the impact of having fewer clinical data sets can be overcome, as demonstrated by models built on nonclinical data and more limited clinical data for newly emerging pathogens, such as SARS-CoV-2 [ 33 , 34 ]…”