Neutralizing activity of BBIBP-CorV vaccine-elicited sera against Beta, Delta and other SARS-CoV-2 variants of concern

Abstract

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the generation of variants that may diminish host immune responses to vaccine formulations. Here we show a registered observational clinical trial (NCT04795414), we assess the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine BBIBP-CorV in a cohort of 1006 vaccine recipients. No serious adverse events are observed during the term of the study. Detectable virus-specific antibody is measured and determined to be neutralizing in 698/760 (91.84%) vaccine recipients on day 28 post second vaccine dose and in 220/581 (37.87%) vaccine recipients on day 180 post second vaccine dose, whereas vaccine-elicited sera show varying degrees of reduction in neutralization against a range of key SARS-CoV-2 variants, including variant Alpha, Beta, Gamma, Iota, and Delta. Our work show diminished neutralization potency against multiple variants in vaccine-elicited sera, which indicates the potential need for additional boost vaccinations.

Fig. 1. Study profile.

*Participants who were administered the vaccination and completed all safety visits, but did not have blood samples taken upon personal request. ^†290 participants who showed negative neutralizing activity against the wild-type strain or who refused to undergo testing the neutralization assay against multiple variants on day 28 after the second dose were excluded. ^‡361 participants with negative neutralizing activity against the wild-type strain on day 180 after the second dose were excluded.

Fig. 2. SARS-CoV-2 specific antibody and neutralizing antibody responses.

a Specific antibodies against SARS-CoV-2 in 964 vaccine recipients on day 21 after the first dose (V3), 760 vaccine recipients on day 28 after the second dose (V4), and 581 vaccine recipients on day 180 after the second dose (V5). The shaded portions indicate two categories of reference values: SARS-CoV-2 specific antibody levels of 571 naive individuals (Naive) and 16 convalescent sera collected at sixth-month post symptom onset from COVID-19 recovered patients (Convalescent). The horizontal dashed line represents the lower limit of detection for the assay (>1). Error bars indicate median and interquartile range (IQR). b The results of 50% pseudovirus neutralization titer (pVNT50) against the wild-type strain in 760 vaccine recipients on day 28 after the second dose (V4), and 581 vaccine recipients on day 180 after the second dose (V5). The shaded portion indicates the category of control values: 50% pseudovirus neutralization titer (pVNT50) against the wild-type strain from 16 convalescent COVID-19 patients. The horizontal dashed line represents the lower limit of detection for the assay (>4). Error bars represent the geometric mean with the 95% confidence interval (95% CI). The exact p values (two-sided) were calculated using the Mann–Whitney U test. No adjustment was done for multiple comparison. Source data are provided as a Source data file.

Fig. 3. Neutralizing antibody responses against multiple SARS-CoV-2 variants.

a Results of 50% pseudovirus neutralization titer (pVNT50) in 470 vaccine recipients on day 28 after the second dose against multiple SARS-CoV-2 variants, including Alpha (p < 0.0001), Beta (p < 0.0001), Gamma (p < 0.0001), and Iota (p < 0.0001) variants compared with the wild-type strain. b Results of 50% pseudovirus neutralization titer (pVNT50) in 220 vaccine recipients on day 180 after the second dose against Delta (p < 0.0001) compared the wild-type strain. c Results of 50% pseudovirus neutralization titer (pVNT50) in 16 convalescent COVID-19 patients against multiple SARS-CoV-2 variants, including Alpha (p = 0.0151), Beta (p = 0.0005), Gamma (p = 0.0034), Delta (p = 0.0054), and Iota (p = 0.0151) variants compared with the wild-type strain. Each vertical bar represents the geometric mean with the 95% confidence interval (95% CI). The fold-changes in geometric mean titer are shown above. The horizontal dashed line represents the lower limit of detection of the assay (>4). The exact p values (two-sided) were calculated using the Wilcoxon matched-pairs signed-rank test. No adjustment was done for multiple comparison. Source data are provided as a Source data file.

Fig. 4. Cross-reactivity of neutralizing antibodies against four variants.

Different colors indicate four different SARS-CoV-2 variants: green, yellow, blue, and red indicate the Alpha, Beta, Gamma, and Iota variants, respectively. Numbers on the diagram indicate the number of participants with positive neutralizing activity against each variant.

Fig. 5. Dynamic changes in the levels of key inflammatory cytokines.

a–h Levels of key inflammatory cytokines including interferon-γ (IFN-γ), interleukin (IL)-10, IL-12p70, IL-13, IL-2, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured in 154 vaccine recipients on the day of the first dose (V2), on day 21 after the first dose (V3), and on day 28 after the second dose (V4). Box plots indicate the median and interquartile range (IQR). The exact p values (two-sided) were calculated using the Wilcoxon signed-rank test. IL: interleukin. No adjustment was done for multiple comparison. Source data are provided as a Source data file.

Fig. 6. Levels of key inflammatory cytokines in relation to neutralizing antibody responses.

a–h Levels of key inflammatory cytokines including interferon-γ (IFN-γ), interleukin (IL)-10, IL-12p70, IL-13, IL-2, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) on the day of the first dose (V2), on day 21 after the first dose (V3), and on day 28 after the second dose (V4) according to neutralizing antibody responses. Blue dots indicate 139 vaccine recipients with positive neutralizing activity on day 28 after the second dose. Yellow dots indicate 15 vaccine recipients with negative neutralizing activity on day 28 after the second dose (V4). Box plots indicate the median and interquartile range (IQR). The exact p values (two-sided) were calculated using the Mann–Whitney U test. IL: interleukin. No adjustment was done for multiple comparison. Source data are provided as a Source data file.