Diminished antibody response against SARS-CoV-2 Omicron variant after third dose of mRNA vaccine in kidney transplant recipients

Abstract

Background: Available SARS-CoV-2 vaccines have reduced efficacy against the Omicron variant in immunocompetent individuals. Kidney transplant recipients (KTRs) have diminished antiviral responses to wild-type SARS-CoV-2 after vaccination, and data on antiviral responses to SARS-CoV-2 variants, including the Omicron variant, are limited. Methods: We conducted a prospective, multi-center cohort study of 51 adult KTRs who received three doses of BNT162b2 or mRNA-1273. Blood and urine samples were collected before and four weeks after the third vaccine dose. The primary outcome was anti-viral antibody responses against wild-type and variants of SARS-CoV-2. Secondary objectives included occurrence of breakthrough SARS-CoV-2 infection and non-invasive monitoring for rejection using serum creatinine, proteinuria, donor-derived cell-free DNA and donor-specific antibodies. Sera from pre-pandemic healthy controls and KTRs were used for comparison. Results: 67% of KTRs developed anti-wild-type spike antibodies after the third vaccine dose, similar to the Alpha (51%) and Beta (53%) variants, but higher than the Gamma (39%) and Delta (25%) variants. No KTRs had neutralizing responses to the Omicron variant before the third vaccine dose. After the third dose, fewer KTRs had neutralizing responses to the Omicron variant (12%) compared to wild-type (61%) and Delta (59%) variants. Three patients (6%) developed breakthrough SARS-CoV-2 infection at a median of 89 days. No KTRs developed allograft injury, de novo donor-specific antibodies or allograft rejection. Conclusion: In KTRs, a third dose of mRNA vaccines increases antibody responses against wild-type and variants of SARS-CoV-2, while neutralizing responses to the Omicron variant remain markedly reduced.

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…However, importantly, two recent studies demonstrated that 25-68% of solid organ transplant recipients had detectable neutralizing Ab against the Delta variant after the third dose of mRNA vaccine (versus 100% of healthy controls) (143,144). Further, none of 51 kidney transplant recipients had detectable neutralizing Ab against the Omicron variant (144).…”

Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients

“…Different studies have shown the seroprotection rates are under 20% after the first dose, and less than 50% after the second one, while in the general population, these values are close to 100% ( 1 – 3 ). Although an improvement in the humoral response has been observed after a third (booster) dose, the seroconversion rate varies from 55 to 67% which is still lower than the observed in the general population ( 4 – 6 ).…”

Humoral Responses in the Omicron Era following Three-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients

“…Importantly, receipt of a third vaccine yielded a significant increase in the proportion of patients with neutralizing capacity against the WT, Beta, Delta and Omicron variants after one month; however, this response was inferior to that observed in healthy controls. Data on the development of an Omicron-specific neutralizing response among KTRs are limited, with rates of 12% (37) and 43% (38) reported at one month. We detected neutralizing antibody to Omicron in over 45% of our cohort at one month, with sustained response in 38.5% at three months following the third mRNA vaccine dose.…”