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

COV-AD consortium

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

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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
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

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)

fimmu-13-912571Final published version, 1.26 MBLicence: Creative Commons: Attribution (CC BY)

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

Cite this

@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",

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",

}

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

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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

UN SDGs

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Projects

COV-AD: Covid infection in patients with antibody deficiency

NIHR Biomedical Research Centre (BRC) - Core Theme

Cite this