Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response - 05/03/25

Doi : 10.1016/j.jinf.2025.106436

C.C.A. Noble ^a,^b,^{^{1
ORCiD: 0000-0003-2503-2976},}^⁎ , E. McDonald ^b,^{^{2
ORCiD: 0000-0003-2295-4641}} , S. Nicholson ^c,^{^{3
ORCiD: 0000-0001-6585-7150}} , S. Biering-Sørensen ^b , L.F. Pittet ^a,^b,^d,^{^{4
ORCiD: 0000-0002-2395-4574}} , A.L. Byrne ^e,^f,^g,^{^{5
ORCiD: 0000-0003-0789-5161}} , J. Croda ^h,^i,^j,^{^{6
ORCiD: 0000-0002-6665-6825}} , M. Dalcolmo ^k,^{^{7
ORCiD: 0000-0002-6820-1082}} , M.V.G. Lacerda ^l,^m,^n,^{^{8
ORCiD: 0000-0003-3374-9985}} , M. Lucas ^o,^p,^q,^r,^{^{9
ORCiD: 0000-0001-8881-9990}} , D.J. Lynn ^s,^t,^{^{10
ORCiD: 0000-0003-4664-1404}} , C. Prat Aymerich ^u,^v,^{^{11
ORCiD: 0000-0001-6974-9165}} , P.C. Richmond ^r,^w,^x,^{^{12
ORCiD: 0000-0001-7562-7228}} , A. Warris ^y,^z , N. Curtis ^a,^b,^aa,^{^{13
ORCiD: 0000-0003-3446-4594}} , N.L. Messina ^a,^b,^{^{14
ORCiD: 0000-0001-8404-4462}}
the BRACE Trial Consortium Group^¹⁵
^‬Members of the BRACE trial Consortium are listed in the Supplementary Appendix.
^a Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
^b Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia
^c Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
^d Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
^e St Vincent's Hospitals Sydney, Darlinghurst, New South Wales, Australia
^f Partners in Health, Socios En Salud, Peru
^g Thoracic Society of Australia & New Zealand (NSW/ACT Branch), Australia
^h Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
ⁱ Fiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz, Campo Grande, Brazil
^j Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil
^k Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil
^l Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil
^m Instituto Leônidas & Maria Deane, Oswaldo Cruz Foundation Ministry of Health, Manaus, Brazil
ⁿ University of Texas Medical Branch, Galveston, TX, USA
^o Department of Immunology, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia
^p Department of Immunology, Perth Children's Hospital, Nedlands, Western Australia, Australia
^q Department of Immunology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
^r School of Medicine, University of Western Australia, Perth, Western Australia, Australia
^s Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
^t Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia
^u University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands
^v ECRAID, European Clinical Research Alliance on Infectious Diseases, Utrecht, the Netherlands
^w Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia
^x Department of Immunology and General Paediatrics, Perth Children's Hospital, Nedlands, Western Australia, Australia
^y Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom
^z Department of Infectious Diseases, Great Ormond Street Hospital, London, United Kingdom
^aa Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia

^⁎Correspondence to: Infectious Diseases Group, Murdoch Children’s Research Institute, 50 Flemington Rd., Parkville, Victoria 3052, Australia.Infectious Diseases Group, Murdoch Children’s Research Institute, 50 Flemington RdParkvilleVictoria3052Australia

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Summary

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.

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Highlights

•	Nucleocapsid protein (N) antibody responses after COVID-19 are variable but persistent.
•	Prior spike-based vaccines reduce seroconversion and anti-N responses after COVID-19.
•	Anti-N levels are higher in those with severe symptoms, older age and comorbidities.
•	Rate of anti-N decline after COVID-19 is determined by the maximum antibody level.
•	Variable anti-N responses to CoronaVac vaccination with lower levels than infection.

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

Plan

Introduction

Materials and methods

Data collection

SARS-CoV-2 serology testing

Inclusion and exclusion criteria

Data analysis

Results

Participants with a confirmed episode of COVID-19

Discussion

Seroconversion following COVID-19 and the influence of prior COVID-19 spike-based vaccination

Antibody kinetics following COVID-19

Antibody response following CoronaVac

Future N protein-based vaccines

Strengths and limitations

Ethics approval

Role of funding source

Funding

Author contributions

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Vol 90 - N° 3

Article 106436- mars 2025 Retour au numéro

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Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response - 05/03/25

Summary

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Methods

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Plan

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