Elizabeth Fraley1, Cas LeMaster1, Eric Geanes1, Dithi Banerjee2, Santosh Khanal1, Elin Grundberg1,3,4, Rangaraj Selvarangan5,6, Todd Bradley7,8,9,10. 1. Genomic Medicine Center, Children's Mercy Research Institute, Children's Mercy Kansas City, Kansas City, MO, 64108, USA. 2. Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO, 64108, USA. 3. Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO, 64108, USA. 4. Department of Pediatrics, UMKC School of Medicine, Kansas City, MO, 64108, USA. 5. Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO, 64108, USA. rselvarangan@cmh.edu. 6. Department of Pediatrics, UMKC School of Medicine, Kansas City, MO, 64108, USA. rselvarangan@cmh.edu. 7. Genomic Medicine Center, Children's Mercy Research Institute, Children's Mercy Kansas City, Kansas City, MO, 64108, USA. tcbradley@cmh.edu. 8. Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO, 64108, USA. tcbradley@cmh.edu. 9. Department of Pediatrics, UMKC School of Medicine, Kansas City, MO, 64108, USA. tcbradley@cmh.edu. 10. Departments of Pediatrics and Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA. tcbradley@cmh.edu.
Abstract
BACKGROUND: The 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. METHODS: We 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. RESULTS: Antibody 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. CONCLUSION: These 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.
BACKGROUND: The 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. METHODS: We 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-2spike protein peptide arrays. RESULTS: Antibody 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-2spike S1 and S2 subunits after vaccination. CONCLUSION: These 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-2spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.
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