Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination

Rafael Ramiro De Assis ,Milind Vasudev,Connie Au,D Huw Davies,Sina Hosseinian,Brandon Chin,Paramveer S Birring,Rana Andary,Sebastian Schubl,Bruce Albala,Anton M Palma ,Rie Nakajima,Anthony H Chau ,Saahir Khan,Amanda Leung,Algis Jasinskas,Joshua M Obiero,Delia F Tifrea ,Jessica Escobar ,Gamal Khalil ,Bernadette Boden‐Albala ,Christina Grabar,Fjolla Muqolli,Aarti Jain,Jenny Ventura,Kendall G Powers ,Daniel M Parker,Philip L Felgner

doi:10.1038/s41541-021-00396-3

Rafael Ramiro De Assis , Milind Vasudev + Show 26 more

Open Access

https://doi.org/10.1038/s41541-021-00396-3

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Abstract

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

Highlights

Protective efficacy of SARS-CoV-2 spike mRNA vaccines reported by the developers, Pfizer and Moderna, has been successful, showing convincing evidence of protection as short as 14 days after the first immunization[1,2]
To further understand the mRNA vaccine induced immune response we were interested to compare the antibody response induced by the vaccine with that induced by natural exposure to SARS-CoV-2
Beginning in March 2020 this study was designed to track the seroprevalence at University of California Irvine Medical Center (UCIMC) healthcare workers (HCW) and the Orange County community residents during the outbreak. (Table 1)

Summary

Introduction

Protective efficacy of SARS-CoV-2 spike mRNA vaccines reported by the developers, Pfizer and Moderna, has been successful, showing convincing evidence of protection as short as 14 days after the first immunization[1,2]. We show results using a multiplex solid phase immunofluorescent assay for quantification of human antibodies against 37 antigens from SARS-CoV-2, other novel and common coronaviruses, and influenza viruses that are causes of respiratory infections (Fig. 1)[5–9]. This coronavirus antigen microarray (COVAM) assay uses a small volume of blood derived from a finger stick, does not require the handling of infectious virus, quantifies the level of different antibody types in serum and plasma and is amenable to scaling-up. Since the assay requires 1 microliter of blood it is practical for monitoring immunogenicity in neonates, children, and small animal models

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