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Alternative Strategies to Increase the Immunogenicity of Covid-19 Vaccines in Kidney Transplant Recipients Not Responding to Two or Three Doses of an mRNA Vaccine. A Randomized Clinical Trial
31 Pages Posted: 29 Jul 2022More...
Background: An urgent need exists to improve the suboptimal COVID-19 vaccine response in kidney transplant recipients (KTR). We compared three alternative strategies with a control single dose mRNA-1273 vaccination: a double vaccine dose, heterologous vaccination and temporary discontinuation of mycophenolate mofetil or mycophenolic acid (MMF/MPA).
Methods: This prospective, multicentre, open-label randomized trial, enrolled KTR without seroconversion after two or three doses of an mRNA vaccine. Between October 20, 2021 and February 2, 2022, 230 KTR were randomized to receive 100 µg mRNA-1273, 2x 100 µg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTR receiving 100 µg mRNA-1273, were randomized to continue (MMF+) or discontinue (MMF-) MMF/MPA treatment for two weeks. Primary outcome was the percentage of participants with an S1-specific IgG concentration ≥ 10 BAU/mL at 28 days after vaccination. Trial registration number: NCT05030974, ClinicalTrials.gov, closed.
Findings: Seroresponse rates did not differ between single mRNA-1273 (69%), double mRNA-1273 (68%), and Ad26.COV2-S (63%), nor between the MMF+ (67%) and MMF- (80%) groups. Neutralizing antibody levels against the SARS-CoV-2 ancestral, Delta and Omicron (BA.1) variants correlated with S1-specific IgG levels (P<0.001) and did not differ between groups. T-cell response rates also did not differ between single mRNA-1273 (52·4%), double mRNA-1273 (52·4%), and Ad26.COV2-S (28·6%), nor between MMF+ (66·7%) and MMF- (54·2%) groups. Local adverse events were more frequent after a single and double dose of mRNA-1273 than after Ad26.COV2-S (91%, 93% and 49%, respectively; P<0·001).
Interpretation: Repeated vaccination increases SARS-CoV-2-specific antibodies and T-cell responses in KTR, without further enhancement by using a higher dose, a heterologous vaccine, or two weeks discontinuation of MMF/MPA. To achieve a stronger response, possibly required to neutralize new virus variants, repeated booster vaccination is needed, and perhaps longer discontinuation of MMF/MPA.
Trial Registration Details: This study was registered in www.ClinicalTrials.gov (NCT05030974).
Funding Information: The study is funded by The Netherlands Organization for Health Research and Development (ZonMW, project number: 10430072010002) and Dutch kidney foundation (project number: 21OP+036).
Declaration of Interests: We declare no competing interests.
Ethics Approval Statement: Ethical approval was obtained from the Dutch Central Committee on Research Involving Human Subjects (CCMO, NL78963.042.21), the central ethics committee at the UMC Groningen (METC 2021/507), and the local ethics committees of the participating centers.
Keywords: COVID-19, mRNA-1273, Ad26.COV2-S, Vaccine, kidney transplantation, immunogenicity
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