Reduced Immune Response and Neutralizing Antibody Activity to the SARS-CoV-2 Vaccination in Patients With a History of Solid Organ Transplant

Deborah French, PhD; Chui Mei Ong, BS; Paul Patel, PhD; Marisa Zuk, BS; Alan H. B. Wu, PhD

Disclosures

Lab Med. 2022;53(5):514-522. 

In This Article

Abstract and Introduction

Abstract

Objective: Three SARS-CoV-2 vaccinations and boosters are available. We determined whether solid organ transplant patients mounted an immune response to the vaccinations and whether the antibodies had neutralizing activity compared to healthcare worker controls and monoclonal gammopathy patients.

Methods: Remnant plasma was obtained from vaccinated solid organ transplant, allogeneic stem cell transplant, monoclonal gammopathy patients, and healthcare worker controls. Samples positive on a SARS-CoV-2 IgG assay (detects spike protein and nucleocapsid) were run on a SARS-CoV-2 in vitro neutralizing antibody assay and a nucleocapsid-specific SARS-CoV-2 IgG assay.

Results: Only 25% of solid organ transplant patients produced antibodies to SARS-CoV-2 vaccination. Of these, 90% had neutralizing activity against wild type virus, but reduced activity to the variants compared to monoclonal gammopathy patients and healthcare worker controls, particularly the delta variant, for which only 50% had neutralizing antibody activity.

Conclusion: Solid organ transplant patients should consider protecting themselves against future SARS-CoV-2 infection.

Introduction

As of March 3, 2022, the SARS-CoV-2 virus has infected over 441 million people worldwide resulting in >5.9 million deaths.[1] Along with masking and social distancing measures, development, approval, and implementation of vaccines is key to stopping the further spread of highly infectious viral infections. To date, the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccinations were given full US Food and Drug Administration approval on August 23, 2021, and January 31, 2022, respectively. They are both 2-dose vaccines based on mRNA technology. The Johnson and Johnson Janssen vaccine (JNJ-78436735) was given emergency use authorization on February 27, 2021, and is based on a modified adenovirus vector.

Patients who undergo a solid organ or stem cell transplant at any stage of life are required to take medications that suppress the immune system to prevent rejection of the transplanted organ or cells. However, this leaves the patients vulnerable to infection. From a study in the United Kingdom, having a solid organ transplant was associated with greater than 3 times increased risk of death from COVID-19 after adjustment for age.[2] Due to this degree of immunosuppression, organ transplant patients were prioritized to have earlier access to the vaccines should they wish to receive them.

As can be appreciated, immunocompromised individuals may have a lower immune response to vaccinations. In a study of 242 kidney transplant patients, 28 days after the first dose of the Moderna vaccine, only 10.8% of these patients had a positive IgG serology test.[3] This was further confirmed in another study of 436 transplant patients that were a median of 20 days postvaccination with either the Pfizer or Moderna vaccine where only 17% of patients had a detectable antibody response.[4] These authors also found that an antibody response to the vaccines was less likely in transplant patients receiving antimetabolite maintenance immunosuppression therapy (mycophenolate) than in transplant patients receiving other types of therapy.[4] It should be noted, however, that 20 or 28 days may not be a sufficient time period in which to mount an adequate immune response. In a follow-up study, the authors investigated the antibody response in 658 solid organ transplant patients after both doses of the vaccine.[5] They found that 15% of these patients had an antibody response after dose 1 and dose 2 of the vaccine, 46% of these patients had no antibody response after either dose, and 39% had no antibody response after dose 1 but developed an antibody response after dose 2 of the vaccine. The previous finding that patients receiving antimetabolite therapy were less likely to have an immune response to the vaccine was mirrored in this study, where 57% of patients taking antimetabolites had no antibody response after doses 1 and 2, 35% had no antibody response after dose 1 but developed one after dose 2, and 8% of patients had an antibody response after dose 1 and dose 2.[5]

In a liver transplant–specific study of 161 patients, it was found that antibodies were detectable in 34% of patients after dose 1 (median of 21 days postdose) and 81% after dose 2 at a median of 30 days after the dose and that 39% of patients receiving 2 vaccine doses on antimetabolite therapy vs 5% not on antimetabolite therapy were nonresponders.[6] A later study investigated B-cell and T-cell responses in 16 solid organ transplant patients vs 23 immunocompetent controls and found that only 37% of solid organ transplant patients vs 100% of immunocompetent controls developed anti-SARS-CoV2 IgG antibodies to the spike protein.[7] Further, only 56% of transplant patients had a detectable T-cell response.[7]

In a previous study of 93 multiple myeloma patients, it was found that 56% had a positive SARS-CoV-2 IgG spike protein antibody response after the first dose of either the Pfizer or Oxford-AstraZeneca (AZD1222; viral vector vaccine) vaccines.[8] In another study,[9] it was found that patients with a history of monoclonal gammopathy had a similar antibody response to the Pfizer, Moderna, and Janssen SARS-CoV-2 vaccines as healthcare worker controls. Therefore, the objective of this study was to investigate the SARS-CoV-2 IgG antibody response in patients who had a history of solid organ or stem cell transplant. Further, this study aimed to determine whether the antibodies that were produced by the transplant patients and patients with a history of monoclonal gammopathy had neutralizing activity towards the different strains of the virus in vitro compared to healthcare worker controls.

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