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

Background: Immunocompromised 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.
Methods: Immunocompromised 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.
Findings: IgG 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.
Conclusions: Saliva conveys vaccine responses induced by mRNA BNT162b2. The predictive power of salivary spike IgG makes it highly suitable for screening vulnerable groups for revaccination.
Funding: Knut 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).
Competing Interests: S. Mielke received honoraria via his institution from Celgene/BMS, Novartis, Gilead/Kite, and DNA Prime for lectures and educational events and as a member and/or head of data safety monitoring boards from Miltenyi Biotec and Immunicum outside the submitted work. K.L. reports grants from Knut and Alice Wallenberg Foundation VC-2021-0018. H.-G.L. reports grants from Knut and Alice Wallenberg Foundation and Nordstjernan AB for studies on COVID-19. P.L. reports grants from Pfizer, grants from MSD, grants and personal fees from Takeda, personal fees from AiCuris, and personal fees from OctaPharma, Enanta Pharmaceuticals, and BMS outside the submitted work. S.A. has received honoraria for lectures and educational events, not related to this work, from Gilead, AbbVie, MSD, Biogen, and Netdoktor and reports grants from Knut and Alice Wallenberg Foundation for this study. M.S.C. reports grants from CIMED for this study and is co-founder of SVF AB.
(© 2022 The Author(s).)