Salivary IgG to SARS-CoV-2 indicates seroconversion and correlates to serum neutralization in mRNA-vaccinated immunocompromised individuals

Katie Healy,Davide Valentini,Cecilia Hellström,Elisa Pin,Sandra Muschiol,Ola Blennow,Anders Österborg,Peter Nilsson,Soo Aleman,Margaret Sällberg Chen,Giorgio Gabarrini,Piotr Nowak,Xinling Xu,Karin Loré,Peter Bergman,Per Ljungman,Hassan Alkharaan,Lotta Hansson,Sophia Hober,Marcus Buggert,Jamil Yousef,Mira Akber,Gunnar Söderdahl,Puran Chen,Stephan Mielke,Michał J Sobkowiak ,Khaled Al‐Manei ,Sára Mravinacová ,Angélica Cuapio ,Gordana Bogdanović ,Hans‐Gustaf Ljunggren ,C I Edvard Smith

doi:10.1016/j.medj.2022.01.001

Abstract

BackgroundImmunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves oral cavity, a primary site of infection, is presently unknown.MethodsImmunocompromised patients (n = 404) and healthy controls (n = 82) participated in a prospective clinical trial (NCT04780659) encompassing two doses of the mRNA BNT162b2 vaccine. Primary immunodeficiency (PID), secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL) patients were included. Salivary and serum immunoglobulin G (IgG) reactivities to SARS-CoV-2 spike were measured by multiplex bead-based assays and Elecsys anti-SARS-CoV-2 S assay.FindingsIgG responses to SARS-CoV-2 spike antigens in saliva in HIV and HSCT/CAR-T groups were comparable to those of healthy controls after vaccination. The PID, SOT, and CLL patients had weaker responses, influenced mainly by disease parameters or immunosuppressants. Salivary responses correlated remarkably well with specific IgG titers and the neutralizing capacity in serum. Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded area under the curve (AUC) = 0.95 and positive predictive value (PPV) = 90.7% for the entire cohort after vaccination.ConclusionsSaliva conveys vaccine responses induced by mRNA BNT162b2. The predictive power of salivary spike IgG makes it highly suitable for screening vulnerable groups for revaccination.FundingKnut and Alice Wallenberg Foundation, Erling Perssons family foundation, Region Stockholm, Swedish Research Council, Karolinska Institutet, Swedish Blood Cancer Foundation, PID patient organization of Sweden, Nordstjernan AB, Center for Medical Innovation (CIMED), Swedish Medical Research Council, and Stockholm County Council (ALF).

Highlights

Vaccine development has been a success story of the coronavirus disease 2019 (COVID-19) pandemic
The BNT162b2 vaccine (Comirnaty, Pfizer-BioNTech) relies on novel mRNA technology, where mRNA is packaged into lipid nanoparticles to deliver genetic instructions for human cells to produce the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein.[1]
As presented in the accompanying flowchart (Figure S1), eligible participants had to be SARS-CoV-2 seronegative at baseline and not meet exclusion criteria, such as PCR positivity at any point of the study, missing baseline serum antibody data, or fewer than two vaccine doses

Summary

Introduction

Vaccine development has been a success story of the coronavirus disease 2019 (COVID-19) pandemic. Adult patients with primary immunodeficiency (PID) or secondary immunodeficiency (SID) generally display higher morbidity and mortality rates from COVID-19 than immunocompetent individuals.[9,10,11] The overall infection fatality rates (IFR) for PID and SID have been reported to be as high as 20% (PID) and 33% (SID), compared with less than 1% in the general population.[9] Around six million people worldwide are estimated to live with a PID,[12,13] while SID disorders are frequent consequences of underlying medical conditions, e.g., human immunodeficiency virus (HIV) infection, malignant diseases, or clinical interventions with immunosuppressive drugs.[14] Patients receiving immunosuppression after undergoing hematopoietic stem cell transplantation (HSCT) or specific cellular therapies (e.g., chimeric antigen receptor T cell [CAR-T] cell therapy) or having hematological malignancies often show prolonged virus shedding and transmission dynamics in which shedding of infectious SARS-CoV-2 could be prolonged up to 2 months or more due to weakened immunity.[15,16] Notably, people with compromised immunity have been mostly excluded from large clinical trials addressing mRNA vaccine effectiveness.[2,17] Recent published reports have, indicated weak or absent immune responses in several groups of immunocompromised persons.[18,19,20,21,22]

Objectives

Methods

Results

Discussion

Conclusion