Defective neutralizing antibody response to SARS-CoV-2 in vaccinated dialysis patients

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Abstract

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis (HD) and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive HD patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity, consistent with a delayed affinity maturation of SARS-CoV-2 S-specific B cells. These data indicate that dialysis patients should be considered for an additional boost and other therapeutic strategies, including early immunotherapy with monoclonal antibodies.

Competing Interest Statement

J.B., C.S.-F., F.M., C.S., M.Me., E.A.D.J., N.C., E.C., D.C. A.L., and L.Pi. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. R.K.G. has received consulting fees from Johnson and Johnson and GlaxoSmithKline. The other authors declare no competing interests.

Funding Statement

The project was partially funded by the Swiss Kidney Foundation (to O.G). We acknowledge support from the G2P-UK National Virology consortium funded by MRC/UKRI (grant ref. MR/W005611/1, to R.K.G.).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Blood samples were obtained from 143 dialysis patients and 48 healthcare workers under study protocols approved by the local Institutional Review Boards (Canton Ticino Ethics Committee, Switzerland). Dialysis patients and HCW were recruited from the four public hospitals of the Ente Ospedaliero Cantonale (EOC) in Ticino (Southern Switzerland). All subjects provided written informed consent for the use of blood and blood components (such as PBMCs, sera or plasma).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv



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