Heterologous SARS-CoV-2 Vaccine Booster Doesn't Improve Response in Kidney Recipients

By Lisa Rapaport

December 29, 2021

(Reuters Health) - Kidney transplant recipients have similar outcomes with both heterologous and homologous third SARS-Cov-2 vaccine doses, a randomized clinical trial suggests.

For the trial, researchers randomized 197 kidney transplant patients who didn't have antibodies against the SARS-Cov-2 spike protein after two doses of a mRNA vaccine from Moderna or Pfizer/BioNTech. Patients were randomized 1:1 to receive either a homologous third vaccine dose or a heterologous third dose of the vaccine from Johnson & Johnson, combining mRNA and viral vector vaccines.

The primary endpoint of the trial was seroconversion four weeks after the third vaccine dose; secondary endpoints included neutralizing antibodies and T-cell response assessed by interferon-γ release assays (IGRA).

Overall, 39% of patients had an antibody response after the third vaccine dose, with no statistically significant difference in response rate based on whether the third dose was a mRNA (35%) or vector (42%) vaccine.

"It did not surprise us that the homo- and heterologous strategy was about equally ineffective," said senior study author Dr. Rainer Oberbauer of the Medical University of Vienna in Austria.

Just 22% of seroconverted patients had neutralizing antibodies, the study also found.

In addition, only 17 patients showed a positive T-cell response assessed by IGRA after the third vaccination, researchers report in JAMA Internal Medicine.

When researchers examined what factors might impact vaccine response, they found that patients who received nontriple immunosuppression were significantly more likely to develop antibodies (odds ratio 3.59). Participants were also significantly more likely to demonstrate a vaccine response with longer time after kidney transplant (OR 1.44), and torque teno virus plasma levels (OR, 0.92 per doubling of levels).

Frequency of pain at the injection site was higher with third doses of the mRNA vaccines than with the vector vaccine, although systemic side effects were similar between groups.

The small sample size may have limited the ability to detect statistically significant differences between groups, the study team notes. The inclusion criteria focused only on kidney transplant recipients without a response to the first two mRNA vaccine doses, which may also limit generalizability.

Even so, the results suggest that kidney transplant patients may have similar benefits from either a homologous or heterologous third vaccine dose, Dr. Oberbauer said by email.

"Given our findings the actual choice of vaccine type is irrelevant," Dr. Oberbauer said.

The obligatory medical immunosuppression in kidney transplant patients works as it is supposed to work, by preventing rejection of the transplant, but in the SARS-CoV-2 setting it interferes with gaining immunity via vaccination, Dr. Oberbauer noted.

"The important take home message is, however, that around one-third of patients seroconverted," Dr. Oberbauer added. "Even though their antibody levels were mainly low, these patients will most likely benefit from additional vaccinations."

SOURCE: https://bit.ly/3pzosez JAMA Internal Medicine, online December 20, 2021.