Waning and boosting of functional humoral immunity to SARS-CoV-2

• Type of Material: Article
• Authors: X Tong, Ragon Institute of MGH, MIT, and Harvard; RP McNarmara, Ragon Institute of MGH, MIT, and Harvard; MJ Avendano, Pontificia Universidad Católica de Chile; EF Serrano, Pontificia Universidad Católica de Chile; T García-Salum, Pontificia Universidad Católica de Chile; C Pardo-Roa, Pontificia Universidad Católica de Chile; J Levican, Pontificia Universidad Católica de Chile; E Poblete, Pontificia Universidad Católica de Chile; E Salina, Pontificia Universidad Católica de Chile; A Munoz, Pontificia Universidad Católica de Chile; A Riquelme, Pontificia Universidad Católica de Chile; G Alter, Ragon Institute of MGH, MIT, and Harvard; RA Medina, Pontificia Universidad Católica de Chile
• Language: English
• Date: 2022-07-25
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2022.07.22.501163
• Title of Journal or Parent Work: bioRxiv
• Grant/Funding Information: Work in the Medina laboratory was partially funded by the FONDECYT 1212023 grant from ANID of Chile, the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) and the Center for Research on Influenza Pathogenesis (CRIP), an NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C).; MJA and ES conducted this work as part of their Ph.D. Thesis, under Programa de Doctorado en Ciencias Biológicas mención Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Cátolica de Chile.; MJA was funded by the ANID Becas/Doctorado Nacional 21212258 scholarship and ES was funded by a scholarship from Vicerrectoría de Investigación de la Escuela de Graduados, Pontificia Universidad Católica de Chile.; CPR and JL conducted this work as part of their Postdoctoral grant FONDECYT 3190706 and 3190648, respectively
• Keywords: Receptor-binding domain; Vaccines; Omicron; antibodies; variants of concern; Spike; receptors; CoronaVac

Abstract

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.