Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

C C A Noble¹, E McDonald², S Nicholson³, S Biering-Sørensen⁴, L F Pittet⁵, A L Byrne⁶, J Croda⁷, M Dalcolmo⁸, M V G Lacerda⁹, M Lucas¹⁰, D J Lynn¹¹, C Prat Aymerich¹², P C Richmond¹³, A Warris¹⁴, N Curtis¹⁵, N L Messina¹⁶; BRACE Trial Consortium Group

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: christie.noble@unimelb.student.edu.au.
² Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: ellie.mcdonald@mcri.edu.au.
³ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. Electronic address: suellen.nicholson@mh.org.au.
⁴ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: sofie.sorensen@mcri.edu.au.
⁵ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: laure.pittet@mcri.edu.au.
⁶ St Vincent's Hospitals Sydney, Darlinghurst, New South Wales, Australia; Partners in Health, Socios En Salud, Peru; Thoracic Society of Australia & New Zealand (NSW/ACT Branch), Australia. Electronic address: Anthony.Byrne@svha.org.au.
⁷ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA; Fiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz, Campo Grande, Brazil; Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil. Electronic address: juliocroda@gmail.com.
⁸ Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil. Electronic address: margarethdalcolmo@gmail.com.
⁹ Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; Instituto Leônidas & Maria Deane, Oswaldo Cruz Foundation Ministry of Health, Manaus, Brazil; University of Texas Medical Branch, Galveston, TX, USA. Electronic address: marcuslacerda.br@gmail.com.
¹⁰ Department of Immunology, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia; Department of Immunology, Perth Children's Hospital, Nedlands, Western Australia, Australia; Department of Immunology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Medicine, University of Western Australia, Perth, Western Australia, Australia. Electronic address: michaela.lucas@uwa.edu.au.
¹¹ Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia. Electronic address: david.lynn@sahmri.com.
¹² University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; ECRAID, European Clinical Research Alliance on Infectious Diseases, Utrecht, the Netherlands. Electronic address: cristina.prat@ecraid.eu.
¹³ School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia; Department of Immunology and General Paediatrics, Perth Children's Hospital, Nedlands, Western Australia, Australia. Electronic address: peter.richmond@uwa.edu.au.
¹⁴ Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom; Department of Infectious Diseases, Great Ormond Street Hospital, London, United Kingdom. Electronic address: A.Warris@exeter.ac.uk.
¹⁵ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: nigel.curtis@rch.org.au.
¹⁶ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: nicole.messina@mcri.edu.au.

PMID: 39922387
DOI: 10.1016/j.jinf.2025.106436

Free article

Randomized Controlled Trial

Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

C C A Noble et al. J Infect. 2025 Mar.

Free article

. 2025 Mar;90(3):106436.

doi: 10.1016/j.jinf.2025.106436. Epub 2025 Feb 6.

Authors

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: christie.noble@unimelb.student.edu.au.
² Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: ellie.mcdonald@mcri.edu.au.
³ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. Electronic address: suellen.nicholson@mh.org.au.
⁴ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: sofie.sorensen@mcri.edu.au.
⁵ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: laure.pittet@mcri.edu.au.
⁶ St Vincent's Hospitals Sydney, Darlinghurst, New South Wales, Australia; Partners in Health, Socios En Salud, Peru; Thoracic Society of Australia & New Zealand (NSW/ACT Branch), Australia. Electronic address: Anthony.Byrne@svha.org.au.
⁷ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA; Fiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz, Campo Grande, Brazil; Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil. Electronic address: juliocroda@gmail.com.
⁸ Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil. Electronic address: margarethdalcolmo@gmail.com.
⁹ Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; Instituto Leônidas & Maria Deane, Oswaldo Cruz Foundation Ministry of Health, Manaus, Brazil; University of Texas Medical Branch, Galveston, TX, USA. Electronic address: marcuslacerda.br@gmail.com.
¹⁰ Department of Immunology, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia; Department of Immunology, Perth Children's Hospital, Nedlands, Western Australia, Australia; Department of Immunology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Medicine, University of Western Australia, Perth, Western Australia, Australia. Electronic address: michaela.lucas@uwa.edu.au.
¹¹ Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia. Electronic address: david.lynn@sahmri.com.
¹² University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; ECRAID, European Clinical Research Alliance on Infectious Diseases, Utrecht, the Netherlands. Electronic address: cristina.prat@ecraid.eu.
¹³ School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia; Department of Immunology and General Paediatrics, Perth Children's Hospital, Nedlands, Western Australia, Australia. Electronic address: peter.richmond@uwa.edu.au.
¹⁴ Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom; Department of Infectious Diseases, Great Ormond Street Hospital, London, United Kingdom. Electronic address: A.Warris@exeter.ac.uk.
¹⁵ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: nigel.curtis@rch.org.au.
¹⁶ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: nicole.messina@mcri.edu.au.

PMID: 39922387
DOI: 10.1016/j.jinf.2025.106436

Abstract

Objectives: SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac.

Methods: Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac.

Results: In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices.

Conclusions: Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.

Keywords: Anti-N; Antibody; COVID-19; CoronaVac; Nucleocapsid protein; SARS-CoV-2; Seroconversion; Vaccination.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The trial is financially supported by the Foundations listed in the Funding section. Authors disclose funding support over the past 36 months: National Health and Medical Research Council (NHMRC) Ideas Grant (NM), NHMRC Investigator Grant (NC). Outside of the submitted work, JC has received grants or contracts from Sanofi, MSD & CEPI; payment or honoraria for presentations from Pfizer and participates on Latin American data safety monitoring/advisory boards for mRNA-1273 (Modern/Zodiac), RSV maternal vaccine (Pfizer), Qdenga vaccine (Takeda) and Nirmatrelvir/Ritonavir- Paxlovid (Pfizer). Outside of the submitted work, PCR has received payment, honoraria or support for lectures, presentations or meeting attendance from GlaxosmithKline, Pfizer, Resvinet Foundation related to meningococcal and pneumococcal diseases and RSV; received research grants or contracts (to institution) from Merck Sharpe & Dohme; participates on Scientific Advisory Boards related to COVID-19, meningococcal, RSV, pneumococcal disease/vaccines; and has a bacteriotherapy patent pending. All other authors declare no conflict of interest.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

Affiliations

Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous