Kinetics of vaccine-induced neutralizing antibody titers and estimated protective immunity against wild-type SARS-CoV-2 and the Delta variant: A prospective nationwide cohort study comparing three COVID-19 vaccination protocols in South Korea

Abstract

IntroductionDespite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy.MethodsWe performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant.ResultsWe conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2–99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7–100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0–87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT).ConclusionDecreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.

Neutralizing activity against Omicron BA.5 after tixagevimab/cilgavimab administration comparable to those after Omicron BA.1/BA.2 breakthrough infections

“…Those who received tixagevimab/cilgavimab 300 mg also exhibited comparable neutralizing activity with these comparators. PRNT ND 50 of 118.25 has been suggested as the 50% protective neutralizing titer in our previous study (12). Since most patients exhibited BA.5 PRNT ND 50 over 118.25 after tixagevimab/cilgavimab administration except for one (ND 50 99.4), the protective role of tixagevimab/ cilgavimab is anticipated during the BA.5 dominant outbreak period.…”

“…For the evaluation of immunity level in healthy adult population when tixagevimab/cilgavimab was introduced in Korea, sera obtained from a heterologous booster shot cohort of healthcare workers (HCWs) were utilized (12). HCWs in this booster shot cohort received a 3 rd dose of mRNA COVID-19 vaccine (BNT162b2; Comirnaty ® , Pfizer, NY, USA) after two standard doses of adenovirus vector (Adv) vaccines (ChAdOx1; Vaxzevria ® , AstraZeneca, Oxford, UK).…”

“…Sera sampled one month after the 3 rd shot (mid-December 2021) and five months after BA.1/BA.2 BI (late July 2022) were used. Follow-up sera from HCWs of the booster shot cohort who did not experience BI were not included in the present comparison, because the antibody titers and neutralizing activities would have waned and would be significantly lower than those of the sera collected one month after the 3 rd shot (12). Since a limited number of HCWs in the booster shot cohort experienced BI during the BA.5 outbreak period, 20 HCWs who received three doses of vaccines (adv/adv/mRNA) and experienced BA.5 BI (after week 32 when BA.5 accounted for more than 90% of domestic cases) were additionally recruited.…”

“…To standardize binding assay results to the binding antibody units (BAU) recommended by the World Health Organization, a correction factor of 0.972 provided by the manufacturer was multiplied to the result (15,16). To the evaluate neutralizing activity against BA.5, PRNT was conducted for the selected specimens (12,17,18). Considering the capacity of biosafety level-3 laboratory and time required for PRNT, 45 specimen were planned for PRNT.…”

Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS‐CoV‐2 Omicron BA.1 and BA.5 variants

“…Since the beginning of the COVID-19 pandemic, measuring neutralizing antibodies against SARS-CoV-2 has been an important investigation to assess protective immunity, herd immunity, and vaccine effectiveness. 4,6,11,12,[24][25][26] Because clinical applications of neutralizing assays with live virus are limited, quantitative immunoassays and sVNT assays have been widely used. 24,27,28 As VOCs have emerged, the performance of previously developed kits based on the WT SARS-CoV-2 has been questioned, and several manufacturers have developed new antibody testing kits based on the emerging VOCs.…”