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

Abstract

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. Results IgG responses to SARS-CoV-2 spike antigens in saliva in HIV and HSCT/CAR-T groups were comparable to 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 AUC=0.95, PPV=90.7% for 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. Findings. 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, Stockholm County Council (ALF).

Characterization of Serum and Mucosal SARS-CoV-2-Antibodies in HIV-1-Infected Subjects after BNT162b2 mRNA Vaccination or SARS-CoV-2 Infection

“…Furthermore, our multivariate linear regression analysis adjusting for age as well as gender, prime-boost interval, and time after second vaccine dose reveals an effect of HIV-1 infection on serum anti-spike IgA and neutralizing antibody levels but not on anti-spike IgG levels. Our findings are different from other studies reporting similar BNT162b2 mRNA-induced serum anti-spike neutralizing antibody levels between HIV-1-infected persons and healthy controls [ 5 , 7 , 40 , 41 ]. Differences in sampling time could account for divergence in findings, with our sampling time up to 7.5 weeks in HIV-1-infected and 9.5 weeks in HIV-1-uninfected as opposed to 1–4 weeks.…”

“…Other groups recently reported mucosal antibodies both after SARS-CoV-2 infection and vaccination. In most of those studies, spike-specific saliva antibodies could be detected at higher frequencies than in our study [ 31 , 35 , 40 , 51 , 52 , 53 ]. This difference could be influenced by the method of saliva sample collection.…”

“…In our study, saliva was sampled by spitting into a collection tube, while other studies utilized oral swabs or mouthwash samples [ 52 ]. In some reports, the saliva samples were concentrated after a centrifugation step [ 52 , 53 ], treated with additives [ 35 ] or heat-inactivated [ 40 ]. Furthermore, different serological assays were used for the measurement of antibodies.…”

Serologic response and safety of COVID-19 vaccination in HSCT or CAR T-cell recipients: a systematic review and meta-analysis

“…MAGLUMI 2019-nCoV IgG chemiluminescent assay (SNIBE—Shenzhen New Industries Biomedical Engineering Co., Ltd., Shenzhen, China) 5. COVID-19 ELISA IgG (Vircell Spain S.L.U., Granada, Spain) Kalpana Parvathaneni [ 41 ] US/2021 2 12 (12) CAR T 8 (8) Healthy controls B-ALL, DLBCL, NHL, MCL, CLL 53 (16–74) 25.0% BNT162b2; mRNA-1273 Up to 28 days Not reported Katie Healy [ 35 ] Sweden/2021 2 74 (69) Allo-HSCT/CAR T 82 (82) Healthy controls Not reported 60 (51–67) 45.0% BNT162b2 14 days Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics); ≥ 0.80 U/mL Lorenzo Canti [ 26 ] Belgium/2021 1 40 (37) Allo-HSCT 40 (40) Healthy controls Not reported 60 (26–76) 52.5% BNT162b2 21 days WANTAI SARS-Cov-2 Ab ELISA (Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) 2 40 (37) Allo-HSCT 40 (40) Healthy controls 28 days Lorenzo Canti-2 [ 39 ] Belgium/2022 3 38 (38) Allo-HSCT No Not reported 60 (26–76) 50.0% BNT162b2 28 days WANTAI SARS-Cov-2 Ab ELISA (Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) …”

Immunizing the imperfect immune system

“…In a follow-up study addressing salivary spike-specific immunoglobulin G (IgG) after vaccination, patients with IEI had weaker salivary responses, although overall salivary titers did correlate with serum neutralizing capacity. 37 Lower seroconversion rates (33% for patients with CVID) were observed by Fernandez et al 38 In the largest case series to date, van Leeuwen et al assessed 505 patients with IEI after vaccination with mRNA-1273. Overall, mild antibody deficiencies and phagocytic defects had similar seroconversion to HCs, whereas more severe IEI, including CVID and combined immunodeficiency (CID), had lower seroconversion rates.…”