ABSTRACT
COVID-19 infection continues to be a health threat particularly to immunocompromised transplant recipients. These patients remain at high risk for the development of severe disease. So, it was imperative to study the humoral response to COVID-19 vaccines in these patient to learn and to establish protocols or policies for the prevention and treatment of their infection. We evaluated 90 sera from 36 heart and 34 from kidney transplant recipients for antibodies to COVID-19 (SARS-COV-2) following first, second or third vaccination. Antibodies were measured by 2 commercial methods of rapid test for qualitative detection of IgM and IgG or by single antigen beads. The latter was for semi-quantitative detection of IgG to RBD (receptor binding protein), S (Spike protein), S1 motif (receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2) and S2 motif (mediates viral RNA to cell membrane fusion) of spike protein. Our finding demonstrates that almost half of the patients had no detectable antibodies by either of the methods. The single antigen beads assay was a better method in detecting antibodies with less false negative as compared to the rapid method. In patients who had developed antibodies to COVID-19, level of antibodies measured by MFI values increased after 2nd and 3rd dose of vaccinations. Of 18 patients who received the 3rd vaccine (first boost), 7 remained to have no detectable antibodies, 5 seroconverted to be positive and the other 6 demonstrated increase in their antibody levels. Interestingly, the titer of antibodies to S2 was lower than RBD, S and S1 and diminished more rapidly. In addition, patients who had both Covid-19 infection and vaccinations had higher level of antibodies to all, including the S2 motif. Furthermore, our data showed that patients with longer transplants demonstrated better humoral response to vaccines. COVID-19 vaccination in immunocompromised solid organ transplant recipients have resulted in detectable antibody response in almost half of the patients which is expected to be protective and prevent severe complications. Our observation supports the need to develop policies for mandatory vaccination prior to transplant as 39% of immunocompromised solid organ transplants had no detectable antibodies even after 3 doses of vaccine. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Purpose: The diverse factors affecting the vaccine induced neutralizing antibody response in solid organ transplant recipients and their immunity against CoV2 variants are needed to be well characterize to understand how we improve the vaccine efficacy. Method(s): Anti-CoV2 receptor binding domain (RBD) plasma antibody response and their neutralization potency in 29 kidney and 22 heart transplant patients was determined with recombinant RBD protein binding ELISA and by calculating the 50% virus neutralization titer of the plasma antibody with ACE2-Hu-HeLa cell based pseudo virus neutralization assay against CoV2 wild type and delta variant. Result(s): We detected strong binding and protective neutralizing plasma antibody response in SOTR who were infected with CoV-2 either prior to or after the first dose of vaccine (n=8), who showed high median IC50 value > 10,000 against both the CoV2 wild type strain and the more transmissible delta variant. In contrast to this, the CoV2 uninfected and vaccinated SOTR ( naive vaccinees, n=43) had considerably lower anti-RBD plasma antibody binding titers, and only 19% of this population possessed minimally protective neutralizing antibody titer (IC50 >50) against the wild type CoV2 strain, which further decreased to 10% against the delta variant. While IgG and IgA were dominant isotypes of anti-RBD antibody induced by the CoV2 vaccines and correlated significantly (r=0.84, p=<0.001) with the CoV2 neutralization. The COV2 uninfected SOTR vaccinees who were within 1.5 years from transplantation or African American ethnicity were less likely to have detectable vaccine induced neutralizing antibody responses than the other populations. In the naive vaccinees, administration of corticosteroids in combination with calcineurin or mTOR inhibitors and antimetabolites also negatively affected the CoV2 antibody responses, while female and younger organ transplant recipients tended towards higher IgM and IgA titers. Kidney transplant recipients showed better IgG responses vs heart transplant recipients and elevated serum creatinine levels correlated with poorer antibody response to the vaccines in both kidney and heart transplant groups. Conclusion(s): These results suggest that in the absence of immunity due to CoV2 infection, vaccination in SOTRs induces much lower protective antibody levels than in healthy controls and identifies African-American ethnicity, less than 1.5 years post transplantation as additional risk factors that further exacerbate these effects. Poor kidney function negatively affected the vaccine induced antibody response.