Neutralizing antibody titers six months after Comirnaty vaccination: kinetics and comparison with SARS-CoV-2 immunoassays.

mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses. A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t12) and 28 (t28) days, and 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT). The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1-92.8%) for S-RBD IgG, 82% (58.6-89.3%) for trimeric-S, 70.4% (34.5-86.4%) for VNT-Nab, 75% (50-87.5%) for PRNT50 and 75% (50-93.7%) for PRNT90. At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001). After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed.

Padoan A ，Cosma C ，Bonfante F ，Della Rocca F ，Barbaro F ，Santarossa C ，Dall'Olmo L ，Pagliari M ，Bortolami A ，Cattelan A ，Cianci V ，Basso D ，Plebani M ... -  《-》

A cohort analysis of SARS-CoV-2 anti-spike protein receptor binding domain (RBD) IgG levels and neutralizing antibodies in fully vaccinated healthcare workers.

The waning of humoral immunity after COVID-19 vaccine booster (third dose) has not yet been fully evaluated. This study updates data on anti-SARS-CoV-2 spike protein receptor binding domain (S-RBD) binding antibodies (bAb) and neutralizing antibodies (NAb) levels in individuals with homologous vaccination 3-4 months after receiving the booster dose. Fifty-five healthcare workers (HCW) from Padova University-Hospital were asked to collect serum samples for determining antibodies (Ab) at 12 (t12) and 28 (t28) days, at 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation, and 3-4 months after receiving the 3rd homologous booster dose. HCW were monitored weekly for SARS-CoV-2 infection. Ab titers were measured by two chemiluminescent immunoassays, one targeting the S-RBD immunoglobulin G (IgG), and one surrogate viral neutralization test (sVNT), measuring NAb. Twenty of the HCW had natural COVID-19 infection (COVID+) at different times, before either the first or the second vaccination. Median S-RBD IgG and NAb levels and their interquartile ranges 3-4 months after the 3rd dose were 1,076 (529-3,409) kBAU/L and 15.8 (11.3-38.3) mg/L, respectively, for COVID-, and 1,373 (700-1,373) kBAU/L and 21 (12.8-53.9) mg/L, respectively, for COVID+. At multivariate regression analyses, with age and gender included as covariates, S-RBD IgG bAb and sVNT NAb levels were closely associated with the time interval between serological determination and the 3rd vaccine dose (log10 βcoeff=-0.013, p=0.012 and log10 βcoeff=-0.010, p=0.025) for COVID+, whereas no such association was found in COVID- individuals. The third booster dose increases anti-SARS-CoV-2 Ab levels, elevated levels persisting for up to 3-4 months. Waning of Ab levels appears to be less pronounced for COVID+ individuals.

Padoan A ，Cosma C ，Della Rocca F ，Barbaro F ，Santarossa C ，Dall'Olmo L ，Galla L ，Cattelan A ，Cianci V ，Basso D ，Plebani M ... -  《-》

SARS-CoV-2 neutralizing antibodies after one or two doses of Comirnaty (BNT162b2, BioNTech/Pfizer): Kinetics and comparison with chemiluminescent assays.

Studies evaluating neutralizing antibody (NAb) after BNT162b2 vaccine are scarce. We therefore compared NAb using the plaque reduction neutralization test (PRNT) in vaccinated subjects, with those from five chemiluminescent (CLIA) assays, two targeting ACE and S-RBD interaction. Sera from 174 completely Comirnaty/BNT162b2 vaccinated healthcare workers (HCW) were evaluated at t12 and t28. NAb titers at low (PRNT50) or high (PRNT90) stringency were compared with: Liaison SARS-CoV-2 Trimeric-S IgG, Elecsys S-RBD Ab, Maglumi SARS-CoV-2 S-RBD IgG and SARS-CoV-2 Nab; iFlash 2019-nCoV NAb. Neither PRNT50 nor PRNT90 correlated with age (range, 24-65 years); no significant differences were found for gender. PRNT50 and PRNT90 seropositive titers (≥1:20) were 43 (24.7%) and 15 (8.6%) at t12 and 167 (95.9%) and 149 (85.6%) at t28. CLIA results at t28 were uncorrelated with age, apart from Elecsys S-RBD Ab (r = -0.164, p = 0.046). Gender differences were found for Maglumi SARS-CoV-2 S-RBD IgG (p = 0.037) and Maglumi NAb (p = 0.046). Considering PRNT50 at thresholds of 1:20 (or 1:40) and 1:160 (or 1:320), corresponding to different immune protective levels, CLIA cut-offs have been identified. Comirnaty/BNT162b2 elicits strong NAb production, especially 28 days after first inoculum. Differences in correlation between Nab titers and circulating antibodies measured by 5 immunoassays have been found, being stronger the correlation for Maglumi Nab.

Padoan A ，Cosma C ，Bonfante F ，Rocca FD ，Barbaro F ，Santarossa C ，Dall'Olmo L ，Pagliari M ，Bortolami A ，Cattelan A ，Cianci V ，Basso D ，Plebani M ... -  《-》

Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine.

Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide; however, the longevity of vaccine effectiveness is not known. We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5-2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8-4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0-1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Choi JH ，Kim YR ，Heo ST ，Oh H ，Kim M ，Lee HR ，Yoo JR ... -  《Frontiers in Immunology》

Stronger and durable SARS-CoV-2 immune response to mRNA vaccines in 5-11 years old children with prior COVID-19.

Di Chiara C ，Cantarutti A ，Raffaella Petrara M ，Bonfante F ，Benetti E ，Boracchini R ，Bosa L ，Carmona F ，Cosma C ，Cotugno N ，Le Prevost M ，Martini G ，Meneghel A ，Pagliari M ，Palma P ，Ruffoni E ，Zin A ，De Rossi A ，Giaquinto C ，Donà D ，Padoan A ... -  《-》