Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms
<b>Background/Objectives</b>: 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)). <b>Methods:</b> 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. <b>Results</b>: 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. <b>Conclusions</b>: 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.
Authors
- Matthew Graham‐Brown (ORCID: https://orcid.org/0000-0002-6197-180X)
- Sherna Adenwalla (ORCID: https://orcid.org/0000-0002-7717-8099)
- Sian Faustini (ORCID: https://orcid.org/0000-0002-9300-5569)
- Gemma D. Banham (ORCID: https://orcid.org/0000-0002-2134-4596)
- Rachel E. Lamerton (ORCID: https://orcid.org/0000-0002-8931-7279)
- Fiona Ashford (ORCID: https://orcid.org/0000-0002-2946-3864)
- Adam F. Cunningham (ORCID: https://orcid.org/0000-0003-0248-964X)
- Ian R. Henderson (ORCID: https://orcid.org/0000-0002-9954-4977)
- Lorraine Harper (ORCID: https://orcid.org/0000-0003-1343-9234)
- Maddy L. Newby (ORCID: https://orcid.org/0000-0003-0624-245X)
- Alex Richter (ORCID: https://orcid.org/0000-0003-2885-1299)
- Max Crispin (ORCID: https://orcid.org/0000-0002-1072-2694)
- Aleksandra Jasiulewicz (ORCID: https://orcid.org/0000-0002-9189-9319)
- Haresh Selvaskandan (ORCID: https://orcid.org/0000-0002-2874-7005)
- Marisol Pérez-Toledo (ORCID: https://orcid.org/0000-0002-5734-255X)
- Nadezhda Wall (ORCID: https://orcid.org/0000-0001-7732-3498)
- Roseanne E Billany (ORCID: https://orcid.org/0000-0001-9610-4717)
Institutions
- University Hospitals Birmingham NHS Foundation Trust (GB)
- University of Leicester (GB)
- The University of Queensland (AU)
- University Hospitals of Leicester NHS Trust (GB)
- University Hospitals Coventry and Warwickshire NHS Trust (GB)
- National Institute for Health and Care Research (GB)
- NIHR Leicester Biomedical Research Centre (GB)
- University of Southampton (GB)
- University of Birmingham (GB)
Publication Details
- Journal
- Vaccines
- Published
- 2024-12-25
- DOI
- https://doi.org/10.3390/vaccines13010007
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- Wellcome Trust
- Francis Crick Institute
- Polycystic Kidney Disease Charity
- Queen Elizabeth Hospital Birmingham Charity
- Cancer Research UK
- Kidney Research UK
- Medical Research Council