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Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals

BACKGROUND: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who re...

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Autores principales: Pushpakumara, Pradeep D., Jeewandara, Chandima, Bary, Farha, Madushanka, Deshan, Perera, Lahiru, Aberathna, Inoka Sepali, Nimasha, Thashmi, Jayamali, Jeewantha, Ranasinghe, Thushali, Kuruppu, Heshan, Danasekara, Saubhagya, Wijewickrama, Ananda, Ogg, Graham S., Malavige, Gathsaurie Neelika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844014/
https://www.ncbi.nlm.nih.gov/pubmed/36656781
http://dx.doi.org/10.1101/2023.01.05.23284247
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author Pushpakumara, Pradeep D.
Jeewandara, Chandima
Bary, Farha
Madushanka, Deshan
Perera, Lahiru
Aberathna, Inoka Sepali
Nimasha, Thashmi
Jayamali, Jeewantha
Ranasinghe, Thushali
Kuruppu, Heshan
Danasekara, Saubhagya
Wijewickrama, Ananda
Ogg, Graham S.
Malavige, Gathsaurie Neelika
author_facet Pushpakumara, Pradeep D.
Jeewandara, Chandima
Bary, Farha
Madushanka, Deshan
Perera, Lahiru
Aberathna, Inoka Sepali
Nimasha, Thashmi
Jayamali, Jeewantha
Ranasinghe, Thushali
Kuruppu, Heshan
Danasekara, Saubhagya
Wijewickrama, Ananda
Ogg, Graham S.
Malavige, Gathsaurie Neelika
author_sort Pushpakumara, Pradeep D.
collection PubMed
description BACKGROUND: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. METHODS: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19. RESULTS: We identified four immunodominant regions aa 29–52, aa 155–178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. CONCLUSIONS: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.
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spelling pubmed-98440142023-01-18 Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals Pushpakumara, Pradeep D. Jeewandara, Chandima Bary, Farha Madushanka, Deshan Perera, Lahiru Aberathna, Inoka Sepali Nimasha, Thashmi Jayamali, Jeewantha Ranasinghe, Thushali Kuruppu, Heshan Danasekara, Saubhagya Wijewickrama, Ananda Ogg, Graham S. Malavige, Gathsaurie Neelika medRxiv Article BACKGROUND: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. METHODS: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19. RESULTS: We identified four immunodominant regions aa 29–52, aa 155–178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. CONCLUSIONS: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines. Cold Spring Harbor Laboratory 2023-01-07 /pmc/articles/PMC9844014/ /pubmed/36656781 http://dx.doi.org/10.1101/2023.01.05.23284247 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Pushpakumara, Pradeep D.
Jeewandara, Chandima
Bary, Farha
Madushanka, Deshan
Perera, Lahiru
Aberathna, Inoka Sepali
Nimasha, Thashmi
Jayamali, Jeewantha
Ranasinghe, Thushali
Kuruppu, Heshan
Danasekara, Saubhagya
Wijewickrama, Ananda
Ogg, Graham S.
Malavige, Gathsaurie Neelika
Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
title Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
title_full Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
title_fullStr Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
title_full_unstemmed Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
title_short Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
title_sort identification of differences in the magnitude and specificity of sars-cov-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844014/
https://www.ncbi.nlm.nih.gov/pubmed/36656781
http://dx.doi.org/10.1101/2023.01.05.23284247
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