Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

Nadezhda Wall; Rachel Lamerton; Fiona Ashford; Marisol Perez-Toledo; Aleksandra Jasiulewicz; Gemma D. Banham; Maddy L. Newby; Sian E. Faustini; Alex G. Richter; Haresh Selvaskandan; Roseanne E. Billany; Sherna F Adenwalla; Ian R. Henderson; Max Crispin; Matthew Graham-Brown; Lorraine Harper; Adam F. Cunningham

doi:10.3390/vaccines13010007

Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

Nadezhda Wall^*, Rachel Lamerton, Fiona Ashford, Marisol Perez-Toledo, Aleksandra Jasiulewicz, Gemma D. Banham, Maddy L. Newby, Sian E. Faustini, Alex G. Richter, Haresh Selvaskandan, Roseanne E. Billany, Sherna F Adenwalla, Ian R. Henderson, Max Crispin, Matthew Graham-Brown, Lorraine Harper, Adam F. Cunningham

^*Corresponding author for this work

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Abstract

Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)).

Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation.

Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection.

Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

Original language	English
Article number	7
Number of pages	17
Journal	Vaccines
Volume	13
Issue number	1
DOIs	https://doi.org/10.3390/vaccines13010007
Publication status	Published - 25 Dec 2024

Keywords

haemodialysis
antibody
immune responses
SARS-CoV-2
vaccine

UN SDGs

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

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10.3390/vaccines13010007Licence: Creative Commons: Attribution (CC BY)

WallN2024DistinctFinal published version, 2.22 MBLicence: Creative Commons: Attribution (CC BY)

Determining functional immunity to SARS-CoV-2 vaccination and natural infection in haemodialysis patients at high-risk of COVID-19
Banham, G. (Researcher), Richter, A. (Co-Investigator), Stamataki, Z. (Researcher), Harper, L. (Principal Investigator) & Cunningham, A. (Co-Investigator)
Medical Research Council
7/04/21 → 30/06/23
Project: Research Councils

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Wall, N., Lamerton, R., Ashford, F., Perez-Toledo, M., Jasiulewicz, A., Banham, G. D., Newby, M. L., Faustini, S. E., Richter, A. G., Selvaskandan, H., Billany, R. E., Adenwalla, S. F., Henderson, I. R., Crispin, M., Graham-Brown, M., Harper, L., & Cunningham, A. F. (2024). Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms. Vaccines, 13(1), Article 7. https://doi.org/10.3390/vaccines13010007

@article{420a76ac03c7431d85489285f9589bca,

title = "Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms",

abstract = " Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population. ",

keywords = "haemodialysis, antibody, immune responses, SARS-CoV-2, vaccine",

author = "Nadezhda Wall and Rachel Lamerton and Fiona Ashford and Marisol Perez-Toledo and Aleksandra Jasiulewicz and Banham, {Gemma D.} and Newby, {Maddy L.} and Faustini, {Sian E.} and Richter, {Alex G.} and Haresh Selvaskandan and Billany, {Roseanne E.} and Adenwalla, {Sherna F} and Henderson, {Ian R.} and Max Crispin and Matthew Graham-Brown and Lorraine Harper and Cunningham, {Adam F.}",

year = "2024",

month = dec,

day = "25",

doi = "10.3390/vaccines13010007",

language = "English",

volume = "13",

journal = "Vaccines",

issn = "2076-393X",

publisher = "MDPI",

number = "1",

}

Wall, N, Lamerton, R, Ashford, F, Perez-Toledo, M, Jasiulewicz, A, Banham, GD, Newby, ML, Faustini, SE , Richter, AG, Selvaskandan, H, Billany, RE, Adenwalla, SF, Henderson, IR, Crispin, M, Graham-Brown, M, Harper, L & Cunningham, AF 2024, 'Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms', Vaccines, vol. 13, no. 1, 7. https://doi.org/10.3390/vaccines13010007

TY - JOUR

T1 - Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

AU - Wall, Nadezhda

AU - Lamerton, Rachel

AU - Ashford, Fiona

AU - Perez-Toledo, Marisol

AU - Jasiulewicz, Aleksandra

AU - Banham, Gemma D.

AU - Newby, Maddy L.

AU - Faustini, Sian E.

AU - Richter, Alex G.

AU - Selvaskandan, Haresh

AU - Billany, Roseanne E.

AU - Adenwalla, Sherna F

AU - Henderson, Ian R.

AU - Crispin, Max

AU - Graham-Brown, Matthew

AU - Harper, Lorraine

AU - Cunningham, Adam F.

PY - 2024/12/25

Y1 - 2024/12/25

N2 - Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

AB - Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

KW - haemodialysis

KW - antibody

KW - immune responses

KW - SARS-CoV-2

KW - vaccine

U2 - 10.3390/vaccines13010007

DO - 10.3390/vaccines13010007

M3 - Article

C2 - 39852786

SN - 2076-393X

VL - 13

JO - Vaccines

JF - Vaccines

IS - 1

M1 - 7

ER -

Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

Abstract

Keywords

UN SDGs

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Determining functional immunity to SARS-CoV-2 vaccination and natural infection in haemodialysis patients at high-risk of COVID-19

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