Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals

Elizabeth Fraley,Santosh Khanal,Todd Bradley,Cas Lemaster,Eric Geanes,Dithi Banerjee,Rangaraj Selvarangan,Elin Grundberg

doi:10.1186/s12916-021-02055-9

Abstract

BackgroundThe global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection.MethodsWe determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30–60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays.ResultsAntibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination.ConclusionThese findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.

Highlights

The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARSCoV-2 virus
SARS-CoV-2 antibody responses after vaccination in seropositive and seronegative individuals Peripheral blood was collected before vaccination at baseline, after primary immunization, and secondary booster immunization from individuals who had no known history of infection or laboratory-confirmed SARS-CoV-2 infection 30–60 days prior to the administration of the BNT162b2 vaccine
We found that the median median fluorescence intensity (MFI) of the groups (S1, 20.5; S2, 732; RBD, 331.3; nucleocapsid protein (NP), 759.8) in the pre-pandemic individuals were similar to the baseline levels of the seronegative group prior to vaccination

Summary

Introduction

The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARSCoV-2 virus. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection. There is an urgent need to understand humoral immune responses to SARS-CoV-2 and how these responses contribute to disease severity and vaccine-induced immunity. Antibody responses targeting the SARS-CoV-2 spike protein (S) or nucleocapsid protein (NP) are detectable soon after natural infection, within 20 days of symptom onset, and have been demonstrated to be immunoglobulin M (IgM), IgG, and IgA isotypes with varying kinetics of development [3,4,5,6,7]. While IgG and IgM antibody responses have been more extensively studied in SARS-CoV-2 infection, there have been reports that IgA antibodies contribute to the early neutralizing antibody response [8]. Antibodies that can neutralize SARS-CoV-2 and prevent infection are targeted for therapeutics and vaccine development [9, 10]

Methods

Results

Conclusion