Third mRNA Vaccine Dose Boosts Immunity Against SARS-CoV-2 Variants in Transplant Recipients

NEW YORK (Reuters Health) – In organ transplant recipients, a third dose of the Moderna COVID-19 vaccine appears to increase neutralizing antibody response against SARS-CoV-2 variants, according to a new study from Canada.

Variants of concern have supplanted wild-type SARS-CoV-2, but data on two- or three-dose vaccine immunogenicity against these variants are limited, researchers note in Annals of Internal Medicine.

“We show that in organ-transplant recipients, two doses of mRNA-1273 provides very little protection against variants. However, three doses significantly boosts immunity against all the variants tested, including Delta, when compared with a third dose of placebo,” Dr. Atul Humar of the University Health Network in Toronto said. “Of caution though, this immune response is not as robust against the variants as compared with the original SARS-CoV-2 virus. The response against Beta variant is especially poor.”

“However,” Dr. Humar told Reuters Health by email, “the study reinforces the importance of third doses in organ-transplant recipients, even in the face of variants such as Delta.”

To investigate neutralizing antibody responses against SARS-CoV-2 variants in solid-organ-transplant recipients after two and three mRNA-1273 vaccine doses, Dr. Humar and his colleagues conducted a secondary analysis of a double-blind, randomized, controlled trial of a third dose of mRNA-1273 vaccine compared with placebo, at one academic transplant center.

Using a surrogate virus neutralization assay and a spike-pseudotyped lentivirus assay to analyze sera from 117 adult organ-transplant recipients, the researchers assessed neutralization against wild-type virus as well as Alpha, Beta and Delta variants. Sera from the 60 patients in the mRNA-1273 group and from the 57 patients in the placebo group were obtained before and four to six weeks after the third vaccine dose.

After two doses of mRNA-1273 vaccine, the percentage of patients with positive neutralization for all three variants was low compared with wild-type virus. Results of both assays showed that after the third dose, the percentage of patients with positive neutralization response compared with placebo increased for all the variants.

According to the pseudovirus neutralization assay against the Delta variant, 55% patients in the mRNA-1273 group were positive vs. 18% of those in the placebo group. The differences amounted to 36 percentage points for the Alpha variant and 31 percentage points for the Beta variant. Also, in the mRNA-1273 group, variants (especially Beta) showed lower neutralization values compared with wild-type virus.

Overall, the third vaccine dose was safe and well tolerated, and the researchers found no evidence that multiple doses led to acute rejection or graft dysfunction.

“However,” they note, “the relatively small sample and short-term follow-up may preclude detection of a rare safety signal.”

The authors add that these “findings may reasonably be applied to other groups of similarly immunocompromised patients, such as those receiving active cancer chemotherapy or biologics,” and they would like to see further studies in those populations.

Dr. Michael E. de Vera, director of the Loma Linda University Transplant Institute in Loma Linda, California, was not surprised by the findings because “studies have shown booster shots improve protection against COVID-19 in the general population.”

“This study was important to do in order to demonstrate beneficial effects of COVID-19 booster shots in solid-organ-transplant recipients,” Dr. de Vera, who was not involved in the study, told Reuters Health by email. “More and more evidence is pointing to the benefit of receiving booster shots, particularly in immunocompromised, solid-organ-transplant recipients.”

“This is only an in vitro assay study,” he cautioned. “We will have to see if transplant patients who receive booster shots are indeed better protected than those who do not get booster shots.”

The study did not receive commercial funding. The authors and Dr. de Vera report no conflicts of interest.

SOURCE: https://bit.ly/3rqhkCO Annals of Internal Medicine, online November 23, 2021.

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