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Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections

Background: Vaccine mediated SARS-CoV-2 antibody responses should be carefully evaluated. With regular follow-up in healthy individuals, we aimed to determine SARS-CoV-2 serological responses post three doses of immunization and prior to breakthrough infections in the Canadian population. Methods: I...

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Autores principales: Macrae, Kathryn, Gong, Catherine Yuqing, Sheth, Prameet, Martinez-Cajas, Jorge, Gong, Yanping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609966/
https://www.ncbi.nlm.nih.gov/pubmed/36298455
http://dx.doi.org/10.3390/vaccines10101590
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author Macrae, Kathryn
Gong, Catherine Yuqing
Sheth, Prameet
Martinez-Cajas, Jorge
Gong, Yanping
author_facet Macrae, Kathryn
Gong, Catherine Yuqing
Sheth, Prameet
Martinez-Cajas, Jorge
Gong, Yanping
author_sort Macrae, Kathryn
collection PubMed
description Background: Vaccine mediated SARS-CoV-2 antibody responses should be carefully evaluated. With regular follow-up in healthy individuals, we aimed to determine SARS-CoV-2 serological responses post three doses of immunization and prior to breakthrough infections in the Canadian population. Methods: In a prospective cohort study, we enrolled 140 healthy participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor–binding domain were quantified by immunoassay post three doses of immunization. With COVID-19 rapid antigen test, polymerase chain reaction, and whole genome sequencing, 27 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccine (including BNT162b2, AZD1222, and mRNA-1273), the median serum anti-spike protein antibody level was 143.6 BAU/mL (binding antibody unit, interquartile range 79.0–266.6) post the first dose of immunization, 1046.4 BAU/mL (423.9–1738.2) post the second dose, and 1604.7 BAU/mL (700.1–3764.0) post the third dose. Observed differences were significant (p ≤ 0.001). The median antibody level of 1604.7 BAU/mL post third dose is 45.6 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In seven breakthrough cases characterized by whole genome sequencing, prior to infection, antibody concentrations of breakthrough cases were at 3249.4 (Delta), 2748.4 (Delta), 4893.9 (Omicron), 209.1 (Omicron), and 231.5 (Omicron), 725.7 (Omicron), and 2346.6 (Omicron) BAU/mL. Compared with the average antibody concentration of 2057.7 BAU/mL (58 times that of the seroconversion concentration) from above seven cases, 37.2% of triple vaccinated, 19.0% of double vaccinated, and 1.5% single dosed individuals have higher SARS-CoV-2 antibody levels. Conclusions: Most vaccines are effective in producing robust antibody responses when more than one dose is given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants have SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.
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spelling pubmed-96099662022-10-28 Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections Macrae, Kathryn Gong, Catherine Yuqing Sheth, Prameet Martinez-Cajas, Jorge Gong, Yanping Vaccines (Basel) Article Background: Vaccine mediated SARS-CoV-2 antibody responses should be carefully evaluated. With regular follow-up in healthy individuals, we aimed to determine SARS-CoV-2 serological responses post three doses of immunization and prior to breakthrough infections in the Canadian population. Methods: In a prospective cohort study, we enrolled 140 healthy participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor–binding domain were quantified by immunoassay post three doses of immunization. With COVID-19 rapid antigen test, polymerase chain reaction, and whole genome sequencing, 27 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccine (including BNT162b2, AZD1222, and mRNA-1273), the median serum anti-spike protein antibody level was 143.6 BAU/mL (binding antibody unit, interquartile range 79.0–266.6) post the first dose of immunization, 1046.4 BAU/mL (423.9–1738.2) post the second dose, and 1604.7 BAU/mL (700.1–3764.0) post the third dose. Observed differences were significant (p ≤ 0.001). The median antibody level of 1604.7 BAU/mL post third dose is 45.6 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In seven breakthrough cases characterized by whole genome sequencing, prior to infection, antibody concentrations of breakthrough cases were at 3249.4 (Delta), 2748.4 (Delta), 4893.9 (Omicron), 209.1 (Omicron), and 231.5 (Omicron), 725.7 (Omicron), and 2346.6 (Omicron) BAU/mL. Compared with the average antibody concentration of 2057.7 BAU/mL (58 times that of the seroconversion concentration) from above seven cases, 37.2% of triple vaccinated, 19.0% of double vaccinated, and 1.5% single dosed individuals have higher SARS-CoV-2 antibody levels. Conclusions: Most vaccines are effective in producing robust antibody responses when more than one dose is given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants have SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2. MDPI 2022-09-22 /pmc/articles/PMC9609966/ /pubmed/36298455 http://dx.doi.org/10.3390/vaccines10101590 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Macrae, Kathryn
Gong, Catherine Yuqing
Sheth, Prameet
Martinez-Cajas, Jorge
Gong, Yanping
Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
title Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
title_full Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
title_fullStr Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
title_full_unstemmed Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
title_short Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections
title_sort quantitative analysis of sars-cov-2 serological responses post three doses of immunization and prior to breakthrough covid-19 infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609966/
https://www.ncbi.nlm.nih.gov/pubmed/36298455
http://dx.doi.org/10.3390/vaccines10101590
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