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

C C A Noble; E McDonald; S Nicholson; S Biering-Sørensen; L F Pittet; A L Byrne; J Croda; M Dalcolmo; M V G Lacerda; M Lucas; D J Lynn; C Prat Aymerich; P C Richmond; A Warris; N Curtis; N L Messina; BRACE Trial Consortium Group

doi:10.1016/j.jinf.2025.106436

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

J Infect. 2025 Mar;90(3):106436. doi: 10.1016/j.jinf.2025.106436. Epub 2025 Feb 6.

Authors

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

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.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Aged
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
Antibody Formation
COVID-19 Vaccines* / administration & dosage
COVID-19 Vaccines* / immunology
COVID-19* / immunology
COVID-19* / prevention & control
Coronavirus Nucleocapsid Proteins* / immunology
Female
Humans
Male
Middle Aged
Phosphoproteins* / immunology
SARS-CoV-2* / immunology
Seroconversion
Vaccination
Young Adult

Substances

Antibodies, Viral
Coronavirus Nucleocapsid Proteins
nucleocapsid phosphoprotein, SARS-CoV-2
COVID-19 Vaccines
Phosphoproteins