Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

COV-AD consortium; Adrian M Shields; Sian E Faustini; Harriet J Hill; Saly Al-Taei; Chloe Tanner; Fiona Ashford; Sarita Workman; Fernando Moreira; Nisha Verma; Hollie Wagg; Gail Heritage; Naomi Campton; Zania Stamataki; Mark T Drayson; Paul Klenerman; James E D Thaventhiran; Shuayb Elkhalifa; Sarah Goddard; Sarah Johnston; Aarnoud Huissoon; Claire Bethune; Suzanne Elcombe; David M Lowe; Smita Y Patel; Sinisa Savic; Alex G Richter; Siobhan O Burns

doi:10.3389/fimmu.2022.912571

Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

COV-AD consortium, Adrian M Shields^*, Sian E Faustini, Harriet J Hill, Saly Al-Taei, Chloe Tanner, Fiona Ashford, Sarita Workman, Fernando Moreira, Nisha Verma, Hollie Wagg, Gail Heritage, Naomi Campton, Zania Stamataki, Mark T Drayson, Paul Klenerman, James E D Thaventhiran, Shuayb Elkhalifa, Sarah Goddard, Sarah JohnstonAarnoud Huissoon, Claire Bethune, Suzanne Elcombe, David M Lowe, Smita Y Patel, Sinisa Savic, Alex G Richter^*, Siobhan O Burns^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Downloads (Pure)

Abstract

Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.

Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.

Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.

Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).

Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

Original language	English
Article number	912571
Number of pages	9
Journal	Frontiers in immunology
Volume	13
DOIs	https://doi.org/10.3389/fimmu.2022.912571
Publication status	Published - 2 Jun 2022

Bibliographical note

Copyright © 2022 Shields, Faustini, Hill, Al-Taei, Tanner, Ashford, Workman, Moreira, Verma, Wagg, Heritage, Campton, Stamataki, Drayson, Klenerman, Thaventhiran, Elkhalifa, Goddard, Johnston, Huissoon, Bethune, Elcombe, Lowe, Patel, Savic, Richter, Burns and the COV-AD consortium.

Keywords

Antibodies, Viral
Antibody Formation
COVID-19
COVID-19 Vaccines
ChAdOx1 nCoV-19
Humans
SARS-CoV-2
Seroepidemiologic Studies
Vaccination
Viral Vaccines
secondary immunodeficiency
CVID
primary immunodeficiency
inborn errors of immunity
vaccination

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3389/fimmu.2022.912571Licence: Creative Commons: Attribution (CC BY)

ShieldsA2022IncreasedFinal published version, 1.26 MBLicence: Creative Commons: Attribution (CC BY)

COV-AD: Covid infection in patients with antibody deficiency
Shields, A. (Co-Investigator) & Richter, A. (Principal Investigator)
Medical Research Council
1/02/21 → 30/11/22
Project: Research Councils
NIHR Biomedical Research Centre (BRC) - Core Theme
Barrett, T. (Co-Investigator), Adams, D. (Principal Investigator), Newsome, P. (Co-Investigator), Kyte, D. (Co-Investigator), Slade, A. (Co-Investigator) & Calvert, M. (Co-Investigator)
NIHR CENTRAL COMMISSIONING FACILITY
1/04/17 → 30/11/22
Project: Other Government Departments

Cite this

COV-AD consortium, Shields, A. M., Faustini, S. E., Hill, H. J., Al-Taei, S., Tanner, C., Ashford, F., Workman, S., Moreira, F., Verma, N., Wagg, H., Heritage, G., Campton, N., Stamataki, Z., Drayson, M. T., Klenerman, P., Thaventhiran, J. E. D., Elkhalifa, S., Goddard, S., ... Burns, S. O. (2022). Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study. Frontiers in immunology, 13, Article 912571. https://doi.org/10.3389/fimmu.2022.912571

@article{fbec862d3b2f47999f03242b766260b1,

title = "Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study",

abstract = "Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.",

keywords = "Antibodies, Viral, Antibody Formation, COVID-19, COVID-19 Vaccines, ChAdOx1 nCoV-19, Humans, SARS-CoV-2, Seroepidemiologic Studies, Vaccination, Viral Vaccines, secondary immunodeficiency, CVID, primary immunodeficiency, inborn errors of immunity, vaccination",

author = "{COV-AD consortium} and Shields, {Adrian M} and Faustini, {Sian E} and Hill, {Harriet J} and Saly Al-Taei and Chloe Tanner and Fiona Ashford and Sarita Workman and Fernando Moreira and Nisha Verma and Hollie Wagg and Gail Heritage and Naomi Campton and Zania Stamataki and Drayson, {Mark T} and Paul Klenerman and Thaventhiran, {James E D} and Shuayb Elkhalifa and Sarah Goddard and Sarah Johnston and Aarnoud Huissoon and Claire Bethune and Suzanne Elcombe and Lowe, {David M} and Patel, {Smita Y} and Sinisa Savic and Richter, {Alex G} and Burns, {Siobhan O}",

note = "Copyright {\textcopyright} 2022 Shields, Faustini, Hill, Al-Taei, Tanner, Ashford, Workman, Moreira, Verma, Wagg, Heritage, Campton, Stamataki, Drayson, Klenerman, Thaventhiran, Elkhalifa, Goddard, Johnston, Huissoon, Bethune, Elcombe, Lowe, Patel, Savic, Richter, Burns and the COV-AD consortium.",

year = "2022",

month = jun,

day = "2",

doi = "10.3389/fimmu.2022.912571",

language = "English",

volume = "13",

journal = "Frontiers in immunology",

issn = "1664-3224",

publisher = "Frontiers",

}

COV-AD consortium, Shields, AM , Faustini, SE , Hill, HJ, Al-Taei, S, Tanner, C, Ashford, F, Workman, S, Moreira, F, Verma, N, Wagg, H, Heritage, G, Campton, N, Stamataki, Z , Drayson, MT, Klenerman, P, Thaventhiran, JED, Elkhalifa, S, Goddard, S, Johnston, S, Huissoon, A, Bethune, C, Elcombe, S, Lowe, DM, Patel, SY, Savic, S, Richter, AG & Burns, SO 2022, 'Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study', Frontiers in immunology, vol. 13, 912571. https://doi.org/10.3389/fimmu.2022.912571

TY - JOUR

T1 - Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation

T2 - An Update From the COV-AD Study

AU - COV-AD consortium

AU - Shields, Adrian M

AU - Faustini, Sian E

AU - Hill, Harriet J

AU - Al-Taei, Saly

AU - Tanner, Chloe

AU - Ashford, Fiona

AU - Workman, Sarita

AU - Moreira, Fernando

AU - Verma, Nisha

AU - Wagg, Hollie

AU - Heritage, Gail

AU - Campton, Naomi

AU - Stamataki, Zania

AU - Drayson, Mark T

AU - Klenerman, Paul

AU - Thaventhiran, James E D

AU - Elkhalifa, Shuayb

AU - Goddard, Sarah

AU - Johnston, Sarah

AU - Huissoon, Aarnoud

AU - Bethune, Claire

AU - Elcombe, Suzanne

AU - Lowe, David M

AU - Patel, Smita Y

AU - Savic, Sinisa

AU - Richter, Alex G

AU - Burns, Siobhan O

N1 - Copyright © 2022 Shields, Faustini, Hill, Al-Taei, Tanner, Ashford, Workman, Moreira, Verma, Wagg, Heritage, Campton, Stamataki, Drayson, Klenerman, Thaventhiran, Elkhalifa, Goddard, Johnston, Huissoon, Bethune, Elcombe, Lowe, Patel, Savic, Richter, Burns and the COV-AD consortium.

PY - 2022/6/2

Y1 - 2022/6/2

N2 - Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

AB - Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

KW - Antibodies, Viral

KW - Antibody Formation

KW - COVID-19

KW - COVID-19 Vaccines

KW - ChAdOx1 nCoV-19

KW - Humans

KW - SARS-CoV-2

KW - Seroepidemiologic Studies

KW - Vaccination

KW - Viral Vaccines

KW - secondary immunodeficiency

KW - CVID

KW - primary immunodeficiency

KW - inborn errors of immunity

KW - vaccination

UR - http://www.scopus.com/inward/record.url?scp=85132266797&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2022.912571

DO - 10.3389/fimmu.2022.912571

M3 - Article

C2 - 35720400

SN - 1664-3224

VL - 13

JO - Frontiers in immunology

JF - Frontiers in immunology

M1 - 912571

ER -

Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Projects

COV-AD: Covid infection in patients with antibody deficiency

NIHR Biomedical Research Centre (BRC) - Core Theme

Cite this