Passive transfer of Ad26.COV2.S-elicited IgG from humans attenuates SARS-CoV-2 disease in hamsters

Lisa H Tostanoski,Megan Lok,Jingyou Yu,Jerald C Sadoff ,Swagata Kar,Hanneke Schuitemaker,Freek Cox,Maciel Porto,Mathieu Le Gars,Frank Wegmann,Roland Zahn ,Sarah Gardner,Owen Sanborn,Michael S Seaman,Brittany Spence,Kathryn E Stephenson,Danielle Nase,Heath Bradette ,Julia Barrett ,Anne Marit De Groot ,Shivani Patel ,Mark G Lewis ,Hanne Andersen ,Jessica L Ansel ,Kate Jaegle,Aiquan Chang,Abishek Chandrashekar,Daniel Sellers,Catherine Jacob-Dolan,Shaikim Holman,Olivia Powers ,Jeroen Tolboom ,Dirk Heerwegh,Kathleen Cayer,Dan H Barouch

doi:10.1038/s41541-021-00427-z

Abstract

SARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.COV2.S vaccination by adoptive transfer studies. IgG from plasma of Ad26.COV2.S vaccinated individuals was purified and transferred into naïve golden Syrian hamster recipients, followed by intra-nasal challenge of the hamsters with SARS-CoV-2. IgG purified from Ad26.COV2.S-vaccinated individuals provided dose-dependent protection in the recipient hamsters from weight loss following challenge. In contrast, IgG purified from placebo recipients provided no protection in this adoptive transfer model. Attenuation of weight loss correlated with binding and neutralizing antibody titers of the passively transferred IgG. This study suggests that Ad26.COV2.S-elicited antibodies in humans are mechanistically involved in protection against SARS-CoV-2.

Highlights

Pre-clinical studies of candidate SARS-CoV-2 vaccines support spike-specific binding and neutralizing antibody titers as a strong immune correlate of protection[1,2,3,4]
We have previously reported that passive transfer of purified polyclonal IgG from convalescent non-human primates (NHPs) confers protection in the NHP model of SARS-CoV-2 infection in a dose-dependent manner[8] and that spike binding and neutralizing antibodies correlate with protection in the NHP model
We sought to characterize the function of vaccineelicited antibodies from humans in adoptive transfer studies using the SARS-CoV-2 hamster model[10]

Summary

Introduction

Pre-clinical studies of candidate SARS-CoV-2 vaccines support spike-specific binding and neutralizing antibody titers as a strong immune correlate of protection[1,2,3,4]. We have previously reported that passive transfer of purified polyclonal IgG from convalescent non-human primates (NHPs) confers protection in the NHP model of SARS-CoV-2 infection in a dose-dependent manner[8] and that spike binding and neutralizing antibodies correlate with protection in the NHP model. Pre-clinical[1,3,4,9,10] and clinical studies[11,12,13,14] of the Ad26.COV2.S vaccine demonstrated strong immunogenicity, as well as robust protection from severe clinical disease and hospitalization in large-scale efficacy trials[14]. One day post-transfer, hamsters were challenged with WA1/2020 SARS-CoV-2 and monitored for body weight loss as a metric of clinical disease[10] to examine the potential for vaccine-elicited antibodies to attentuate disease severity

Methods

Results

Conclusion