ABSTRACT
Purpose: The impact of antigenic imprinting, when immune memory of one antigen influences the response to subsequent similar antigens, on the antibody response in solid organ transplant recipients (SOTRs) after SARS-CoV-2 vaccination is currently unknown. This study examines the relationship between seasonal coronaviruses (sCoV) and SARS-CoV-2 antibody levels pre- and post-vaccination in SOTRs. Method(s): Plasma from 52 SOTRs pre- and post-SARS-CoV-2 vaccination (2 doses, mRNA) was analyzed using the Meso Scale Diagnostic Coronavirus Panel 3 (an electrochemiluminescence detection-based multiplexed sandwich immunoassay) for IgG antibodies against alpha sCoVs (229E, NL63), beta sCoVs (HKU1, OC43), and SARS-CoV-2 spike proteins. Changes in IgG titers were determined by paired Wilcoxon rank-sum tests. Spearman correlation analysis was used to determine associations between pre-vaccination anti-sCoVs and post-vaccination anti-SARS-CoV-2 IgG. Result(s): Vaccination increased both anti-SARS-CoV-2 (fold change (FC) 1.9, p<0.001) and anti-beta sCoV (HKU1 [FC 0.05, p<0.001], OC43 [FC 0.8, p<0.001]) IgG titers in SOTRs, but did not increase anti-alpha sCoV IgG. Furthermore, prevaccination anti-beta sCoV (HKU1 [rho= -0.3, p=0.03], OC43 [rho= -0.3, p<0.03]) IgG titers were negatively correlated with post-vaccination anti-SARS-CoV-2 IgG. Conclusion(s): These exploratory findings suggest that prior exposure to seasonal betacoronaviruses may lead to antigenic imprinting in SOTRs that negatively impacts the antibody response to vaccination against the novel pandemic betacoronavirus, SARS-CoV-2.
ABSTRACT
Purpose: Humoral response to COVID-19 vaccines is attenuated in many solid organ transplant recipients (SOTRs), necessitating additional primary and booster vaccinations. The omicron variant demonstrates substantial immune evasion, and it is not known if boosters increase neutralizing capacity versus omicron among SOTRs. We therefore investigated SOTR antibody response and neutralization versus variants of concern (VOC) including omicron to a 4th vaccine dose (D4). Method(s): Within a national, prospective observational cohort, 25 SOTRs underwent anti-SARS-CoV-2 spike and receptor binding domain (RBD) IgG testing using the Meso Scale Discovery platform before and 2-4 weeks after D4. Surrogate neutralization (%ACE2 inhibition [%ACE2i], range 0-100% with >20% correlating with live virus neutralization), was measured versus full spike proteins of the ancestral ("vaccine") strain and 5 VOCs including delta and omicron. Change in IgG level and %ACE2i were compared using paired Wilcoxon rank-sum testing. Result(s): Demographics are outlined in Table 1, including median (IQR) age 59 (45- 55) years, 64% kidney recipients, and D4 receipt (60% Moderna, 40% Pfizer) median (IQR) 93 days (28-134) post D3. Two participants had SARS-CoV-2 exposure per anti-nucleocapsid testing, including one incident infection. Overall, anti-RBD (92%- >100%) and anti-spike (84%->92%) seropositivity increased after D4, as did median (IQR) anti-spike IgG 42.3 (4.9-134.2)->228.9 (115.4-655.8) WHO binding antibody units (p<0.05). Median (IQR) %ACE2i significantly increased after D4 vs the vaccine strain 5.8% (0-16.8)->20.6% (5.8-45.9) and delta variant 9.1% (4.9-12.8)->17.1% (10.3-31.7) (both p<0.001). In contrast, no SOTR showed neutralization vs omicron before or after D4: median (IQR) %ACE2i 4.1% (0-6.9)->0.5% (0-5.7) (p=0.11). Conclusion(s): Although a 4th vaccine dose increased anti-spike IgG and neutralizing capacity vs some VOC, there was no omicron variant neutralization among SOTRs. SOTRs may remain at high risk for SARS-CoV-2 infection despite boosting, thus additional protective interventions should be urgently explored. (Figure Presented).