Robust SARS-CoV-2 Antibody Responses in Asian COVID-Naïve Subjects 180 Days after Two Doses of BNT162b2 mRNA COVID-19 Vaccine

Abstract

Background: Subjects with previous COVID-19 have augmented post-vaccination responses. However, the antibody response in COVID-naïve subjects from Southeast Asia is not well known. Methods: 77 COVID-naïve vaccinees were tested with a full antibody panel [spike antibodies (total (T-Ab), IgG, IgM) and neutralizing antibodies (N-Ab)] pre-vaccination, 10 days after dose 1, and 20/40/60/90/120/150/180 days after dose 2. Results: 10 days after dose 1, 67.6% (48/71)/69.0% (49/71) were T-Ab/IgG positive; only 15.5% (11/71)/14.1% (10/71) were N-Ab/IgM positive. While all (100%) subjects had brisk T-Ab, IgG and N-Ab antibody responses 20 days after complete vaccination, only 79.1% (53/67) were IgM positive. At 180 days (n = 8), T-Ab/IgG/N-Ab were still reactive (lowest T-Ab 186 U/mL, IgG 617 AU/mL, N-Ab 0.39 µg/mL), but IgM was negative in all samples. Spike antibody thresholds of T-Ab 74.1 U/mL (r = 0.95) and IgG 916 AU/mL (r = 0.95) corresponded to N-Ab reactivity (>0.3 µg/mL). Non-linear regression analysis showed that N-Ab would decrease to 0.3 µg/mL by 241 days, whereas T-Ab/IgG would need 470/163 days to reach titers of T-Ab/IgG associated with a N-Ab 0.3 µg/mL (76.4 U/mL and 916 AU/mL respectively). Conclusions: The antibody responses of T-Ab, IgG and N-Ab remain high and durable even at 180 days. N-Ab titers are expected to remain reactive up to 241 days post-vaccination.

SARS-CoV-2 Spike and Neutralizing Antibody Kinetics 90 Days after Three Doses of BNT162b2 mRNA COVID-19 Vaccine in Singapore

“…These findings are similar to those reported in other countries [2][3][4][5]. We also confirm the further decline of both S-Ab and N-Ab beyond 180 days after the second dose of mRNA vaccine, extending the of our previous study [12]. The S-Ab/N-Ab titers dropped by 63%/76% between the peak post-second dose levels and prebooster levels.…”

“…The peak post-booster S-Ab titer was 11-fold (25,220 vs. 2235 BAU/mL) higher than the peak antibody response after the second dose of the Pfizer vaccine while N-Ab was 9-fold higher (30.3 vs. 3.52 µg/mL) (see Figure 3). and from our previous study (prior post-second dose population) [12] and are thus different individuals.…”

“…Thawed samples were vortexed before analysis. The Roche Elecsys Anti-SARS-CoV-2 S quantitative double-antigen sandwich electro-chemiluminescent immunoassay (run on the Roche Elecsys e801 auto-analyzer) and the Snibe competitive quantitative N-Ab assay (run on the Snibe Maglumi) have been previously evaluated and described by our laboratory [11,12]. The Snibe N-Ab assay reports a clinical sensitivity of 100% (95% CI 93.69-100) in 57 samples with confirmed SARS-CoV-2 VNT 50 ≥ 20 in their manufacturer's insert.…”

“…We compared the post-booster antibody responses to the post-second vaccine dose responses from our previous data set [12]. The peak post-booster S-Ab titer was 11-fold (25,220 vs. 2235 BAU/mL) higher than the peak antibody response after the second dose of the Pfizer vaccine while N-Ab was 9-fold higher (30.3 vs. 3.52 µg/mL) (see Figure 3).…”

“…At 6 months (180 days) post-booster, the projected levels of S-Ab and N-Ab would be 2671 BAU/mL and 4.83 µg/mL, still well above pre-booster levels of 829 BAU/mL and 0.83 µg/mL, respectively. We also calculated the half-life for total S-Ab and N-Ab from 20-90 days post-second vaccination from our prior data set [12], and total S-Ab had a half-life of 62 days, but N-Ab had a half-life of 48 days (see Supplementary Figure S2).…”