MO975: Immunogenicity to A Third Dose of the Mrna-1273 Vaccine in Kidney Transplant Recipients
Authors: Tsalouchos Aris , Laudicina Selene , Manfredi Mariangela , Ferro Giuseppe , Simone Giuseppina , Semeraro Francesca , Somma Chiara , Mehmetaj Alma , Dattolo Pietro 
Published: May 2022

Abstract

BACKGROUND
Humoral response after two doses of mRNA-based SARS-CoV-2 vaccines is weak in kidney transplant recipients (KTRs) [1]. Of concern, even a third dose of the mRNA-1273 vaccine induced a suboptimal humoral response in a cohort of KTRs who did not respond after two doses [2]. However, the assessment also of the T-cell immune response of mRNA vaccines in KTRs is limited in the literature [3]. Herein, we report the evaluation of humoral response induced after a third dose of the mRNA-1273 vaccine in a cohort of KTRs and T-cell immune responses in not responders to the third dose.

METHODS
Observational cohort data were collected from KTRs actively followed up in our outpatient clinic, with no history of COVID-19 infection, who received a third mRNA-1273 vaccine dose, 6 months after the second dose, as per suggested local policy.
The primary endpoint was the humoral response provided at least 4 weeks after the third dose compared with the humoral response after the second dose.
Anti-S1-RBD IgG antibodies were determined using a fluoroimmunoenzymatic method (Thermo Fisher Scientific), and the quantitative result expressed in BAU/mL (reference interval: &lt;28 Negative; 28–40 Borderline; &gt;40 Positive; linear range between 0.7 and &gt;1632 according to the manufacturer). In seronegative and borderline KTRs after the third dose, an INFγ-release assay (IGRA) [Euroimmun, Lubeck, Germany] was used to detect T-cell immune responses. A patient result was considered negative, borderline and positive when IFNγ values were respectively &lt;100, 100–200 and &gt;200 mIU/mL.

RESULTS
Sixty KTRs received a third dose of the mRNA-1273 vaccine. Overall, we obtained the antibody titre in 57 KTRs at a median of 23 days (IQR: 22–31) after the second dose and 23 days (IQR: 21–26) after the third dose.
After the second dose, positive antibody titres were detectable in 28 KTRs (49%), and 2 KTRs (4%) had a borderline positivity. While after third dose, positive and borderline antibody responses were observed in 40 (70%) and 4 (7%) KTRs, respectively.
Among all 57 KTRs, the median anti-S1-RBD IgG titre significantly increased after the third dose ( 448 versus 39 BAU/mL; P = 0.0018; Mann–Whitney test). While in 28 KTRs already seropositive after the second dose, the median antibody titre increased from 556 to &gt;1632 BAU/mL (P = 0.0285; Mann–Whitney test). Figure 1 shows the kinetics of anti-S1-RBD IgG titres after the second and the third dose for all the 57 KTRs.
Among 17 KTRs with negative and borderline humoral responses after the third dose, IFNγ values were positive and borderline in only 1 (6%) and 1 (6%) KTRs, respectively. The median IFNγ value was 22 mIU/mL (IQR: 0–1014).
The 34 KTRs receiving mycophenolate mofetil (MMF) were less likely to develop adequate immune responses than the 23 KTRs not receiving MMF; 12 KTRs (35%) receiving MMF had no antibody and IFNγ positive response after the third dose in comparison to 4 KTRs (17%) not receiving MMF, and the median anti-S1-RBD IgG titre beyond the two groups after the third dose was statistically different (205 versus &gt; 1632; P = 0.0046; Mann–Whitney test).

CONCLUSIONS
In this study, the third dose of the mRNA-1273 vaccine increases the rate of positive antibody responses in non-responders KTRs after the second dose, and improves the magnitude of these responses in already seropositive KTRs. However, a fraction of KTRs still lacks protective antibody titres and T-cell responses after a third dose, with mycophenolate mofetil to be associated with poor immune responses. Alternative vaccination protocols are needed to protect this high-risk group.