Transplant Trial Watch

Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients: A Randomized Clinical Trial.

Reindl-Schwaighofer, R., et al

JAMA Internal Medicine 2021 [record in progress].


Aims
This study aimed to investigate the effectiveness of a third dose of an mRNA vaccine compared to a vector vaccine in kidney transplant recipients who had not developed antibodies against the SARS-CoV-2 spike protein after two previous doses of an mRNA vaccine.

Interventions
Participants were randomly assigned to receive either an mRNA vaccine( mRNA-1273 or BNT162b2) or a vector vaccine (Ad26COVS1) as a third dose of a SARS-CoV-2 vaccine.

Participants
201 adult kidney transplant recipients without detectable SARS-CoV-2 spike protein antibodies > 4 weeks following the second dose of an mRNA vaccine.

Outcomes
The primary outcome was seroconversion after 4 weeks following the third vaccine dose. Secondary outcomes included neutralizing antibodies and T-cell response.

Follow-up
29 to 42 after vaccination

CET Conclusions
This is a well-written report of a well-conducted randomised controlled trial. In kidney transplant recipients who had not developed an antibody response to 2 previous doses of mRNA SARS-Cov-2 vaccine, the study was conducted to see if a better antibody response could be gained with a third dose of the same type of vaccine or with a vector vaccine (Ad26COVS1). The study was randomised in a 1:1 fashion and single-blinded for the patients. An appropriate cut-off level was set to correlate with antibody neutralizing capacity. The study had excellent follow up and there was no significant difference in response rate to the vaccines (35% for mRNA and 42% for vector vaccine). Applying a higher cut-off predictive for neutralizing antibodies again resulted in no significant difference between the vaccination strategies, but the overall response rate was lower, as one would expect (22%). The antibody levels developed in kidney transplant recipients were lower than in the general population. Triple immune suppression further significantly reduced a patient’s capacity to develop an antibody response. This study shows that kidney transplant recipients at high risk of coronavirus disease, having little or no response to 2 doses of vaccine, can develop a response to a third dose, albeit at a low level and only at potential viral neutralizing level in 22%. This was the same for patients receiving a third dose of mRNA vaccine, or a third dose with a viral vector vaccine.

Jadad score
2

Data analysis
Per protocol analysis

Allocation concealment
No

Trial registration
EudraCT - 2021-002927-39

Funding source
Non-industry funded