key: cord-1041151-kcw33rib
authors: Narasimhan, M.; Mahimainathan, L.; Clark, A. E.; Usmani, A.; Cao, J.; Raj, E.; Torres, F.; Sarode, R.; Kaza, V.; Lacelle, C.; Muthukumar, A.
title: Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines
date: 2021-05-05
journal: nan
DOI: 10.1101/2021.04.26.21255926
sha: e9e9737d3563f8c3b163c721cf524a3a069fc910
doc_id: 1041151
cord_uid: kcw33rib

The immunological effectiveness of SARS-CoV-2 mRNA vaccines in lung transplant (LT) recipients is largely unknown. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccine's two-dose (2D) regimen on humoral responses in immunocompromised lung transplant (LT) recipients. About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6-7.5 AU/mL) compared to non-transplanted, uninfected naive subjects (14209 AU/mL, 95% CI: 11261-18836 AU/mL) (p<0.0001). In LT patients, Moderna-evoked seropositivity trend was higher by 23-fold than Pfizer. 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.

Lung-transplant (LT) recipients are at high risk for severe COVID-19 due to immunosuppression (IS) and respiratory tropism for SARS-CoV-2. Although single dose SARS-CoV-2 vaccine-related immunogenicity in solid organ transplant have emerged 1 , so far there has been no evidence of the impact of 2-dose vaccine regimen on the quality of humoral immunological response in LT recipients. Understanding the impact of vaccine regimens on humoral immunity is critical to optimize the COVID-19 immunization in this immunocompromised cohort.

of either the Pfizer-BioNTech or Moderna vaccines or 2D-vaccinated naïve (nontransplanted and COVID-19 non-exposed) group were used in this study. They were deidentified, discarded, and remnant blood samples available in the laboratory after routine analysis. This study involved no specific collection of samples. The University of Texas Southwestern Medical Center's Institutional Review Board granted a waiver of consent for this study.

Antibody responses were semi-quantitatively assessed using serum samples analyzed on the Alinity i platform (Abbott Laboratories, Abbott Park, IL) using the FDAapproved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgGNC), the SARS-CoV-2 anti-spike protein IgM assay (IgMSP), or the SARS-CoV-2 anti-spike protein IgG II assay (IgGSP) as previously described. 2 Index values of ≥1.4 (IgGNC), ≥ 1.0 (IgMSP), and ≥ 50 AU/ml (IgGSP) were interpreted as positive per the manufacturer's recommended threshold. IgGNC positivity informs natural SARS-CoV-2 infection, while IgGSP/IgMSP positivity strongly correlate with emergence of natural or vaccine-driven neutralizing immunity. 2,3 CD4+ T-cell activity was assessed as a marker of immune competence using All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (Table 1 ; Fig. 1 ). 56 among 73 LT recipients had Cylex Immuknow assay values measured.

Moderna vaccine was found to elicit positive IgGSP responses by 44% (4/9) and 50% (1/2) in the moderate and strong category, respectively. In contrast, the Pfizer vaccine elicited a positive IgGSP response only in 18% (3/17) and none (0/6) in patients with moderate All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 5, 2021. ; https://doi.org/10.1101/2021.04.26.21255926 doi: medRxiv preprint and strong ImmuKnow levels, respectively (Table S1 ). There was no trend for better antibody response for IgGSP, IgMSP, or IgGNC based on Cylex Immuknow assay in both groups.

Comparison of SARS-CoV-2 specific antibody responses following a 2D regimen of mRNA vaccine in LT recipients to non-transplant, immunologically naïve (never SARS-CoV-2 infected) participants clearly illustrated that the median IgGSP levels were significantly lower among immunosuppressed-LT recipients (median of 1.7 AU/mL, 95% CI: 0.6-7.5 AU/mL) compared to naïve individuals (median of 14209 AU/mL, 95% CI: 11261-18836 AU/mL) (p<0.0001; Fig. 2 ). Furthermore, albeit statistically non-significant, a lower circulating IgGSP trend with 2D-Pfizer vaccine was noted than the 2D-Moderna formulation among LT patients ( Fig. S1 ; 23-fold, p=0.9555).

Moderna COVID-19 vaccines following the 2D regimen in LT recipients. Our data shows that only a minority (25%) of the participants mounted appreciable anti-spike antibody responses. In addition, the ImmuKnow Cylex assay-based results suggested that the immune cell function-based stratification does not predict antibody response to the vaccines. However, irrespective of the immune cell function, the Moderna formulation generated a trend towards more robust antibody response than the Pfizer vaccine in immunosuppressed-LT patients, indicating an enhanced protective immunity. The principle of generating a mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation along with the larger dose of 100 µg in the Moderna versus the 30 µg in the Pfizer preparation could explain the differential antibody response obtain when comparing the two vaccines. 4,5 Similar findings were reported All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Importantly, our data indicates that receiving two doses of vaccine does not mean an assured protection against COVID-19 infection for the majority of LT patients, as majority exhibit either nil or negligible IgGSP responses. Evidence from a non-COVID19 context supports the doubling of vaccine dose as an attractive strategy to improve the immunogenicity in transplant recipients. 6 But the theoretical risk of vaccines and alloimmunity and rejection remains, although not a consistent observation so far. It also remains to be evaluated if such lower antibody response early after vaccination would suffice to mitigate risk for COVID-19.

Limitations include small sample size, lack of demographic data in non-transplant group, absence of serial measurements after vaccination, and shorter time for follow up. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Vaccine Regimen in Lung Transplant Patients, Stratified by Cylex ImmuKnow assay levels. + and ─ , Serology assay's positive and negative results based on the manufacturer recommended corresponding cut-off value.

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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 5, 2021. ; https://doi.org/10.1101/2021.04.26.21255926 doi: medRxiv preprint

Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients

Clinical evaluation of the Abbott Alinity SARS-CoV-2 spike-specific quantitative IgG and IgM assays among infected, recovered, and vaccinated groups

The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients

Structure-based design of prefusionstabilized SARS-CoV-2 spikes

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial. Vaccine

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Abbott Diagnostics while provided part of the antibody testing reagents did not have any role in the study's design, collection, analyses, or interpretation of data; drafting manuscript, or in the decision to publish the results. The authors declare no other conflict of interest.

The authors received no financial support for this study.

We thank our medical technologists, Charles Alexis and Kimberly Fankhauser for helping with laboratory testing. We also thank Ashley Comeaux, Ryan Osterberg, Katrina Bolls, All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 5, 2021. ; https://doi.org/10.1101/2021.04.26.21255926 doi: medRxiv preprint

All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 5, 2021. ; https://doi.org/10.1101/2021.04.26.21255926 doi: medRxiv preprint

All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 5, 2021. ; https://doi.org/10.1101/2021.04.26.21255926 doi: medRxiv preprint