Comparison of the immunogenicity of BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong

Abstract

Background and objective: Few head-to-head evaluations of immune responses to different vaccines have been reported.

Methods: Surrogate virus neutralization test (sVNT) antibody levels of adults receiving either two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 [n = 49] vs. CoronaVac [n = 49]) was tested for plaque reduction neutralization (PRNT) and spike-binding antibody and T-cell reactivity in peripheral blood mononuclear cells.

Results: One month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT₅₀ , PRNT₉₀ , sVNT, spike receptor binding, spike N-terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT₅₀ titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45, while PRNT₉₀ titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT_90. Allowing for an expected seven-fold waning of antibody titres over 6 months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT₉₀ antibody titres. Both vaccines induced SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cell responses at 1 month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4⁺ and CD8⁺ T-cell responses.

Conclusion: Vaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induces higher CD4⁺ and CD8⁺ T-cell responses to the structural protein than BNT162b2.

Keywords: BNT162b2; Biontech; COVID-19; CoronaVac; SARS-CoV-2; Sinovac; coronavirus disease; immunogenicity.

FIGURE 1

Antibody responses of individuals before and after BNT162b2 or CoronaVac vaccination. The percentage of inhibition was detected by surrogate virus neutralization test (sVNT) from the plasma collected from adult individuals who received two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) (A). Various antibody responses were further determined from the plasma from an age‐matched subgroup of (A) (49 vs. 49). (B) The percentage of inhibition from the plasma of pre‐vaccination and 1 month after two doses of vaccination was tested by sVNT. The dashed line at 30% indicates the negative threshold of the sVNT. Comparison of the (C) PRNT₅₀ (plaque reduction neutralization test) and (D) PRNT₉₀ from the plasma collected at 1 month after two doses of vaccination between the BNT162b2 and CoronaVac groups. The levels of (E) receptor binding domain‐specific (F) N‐terminal domain‐specific and (G) S2‐specific IgG antibodies from the plasma of pre‐vaccination and 1 month after two doses of vaccination were tested by ELISA. ****p < 0.0001

FIGURE 2

FcγRIIIa‐binding antibodies and IgG avidity in the BNT162b2 and CoronaVac groups. The levels of FcγRIIIa‐binding antibodies and their avidity were detected from the plasma collected from adult individuals who received two doses of BNT162b2 (n = 49) or CoronaVac (n = 49). Recovered COVID‐19 cases (n = 34, timepoint 56 ± 17 days post infection [mean ± SD]) and healthy adults negative for SARS‐CoV‐2 (n = 40) served as positive and negative controls, respectively. The levels of (A) FcγRIIIa‐binding S antibodies and (B) FcγRIIIa‐binding N antibodies were tested from the plasma collected before and at 1 month after two doses of vaccination. The avidity indexes of (C) S FcγRIIIa, (D) S IgG and (E) N FcγRIIIa were determined as the proportion of antibodies remaining after 3× washes with 8 M urea compared to the total FcγRIIIa‐binding antibodies to each protein. ***p < 0.001; ****p < 0.0001

FIGURE 3

T‐cell responses post vaccination are comparable between BNT162b2 and CoronaVac. PBMCs from pre‐ (Day 0) and post‐vaccination (Day 30 after the second dose) of BNT162b2 mRNA (pre‐vaccination n = 25, post‐vaccination n = 25) and CoronaVac (pre‐vaccination n = 30, post‐vaccination n = 30) and recovered COVID‐19 cases (n = 10, timepoint 59 ± 20 days post infection [mean ± SD]) were stimulated with pooled structural (S, N, Envelope and Matrix [SNEM]) peptides or a dimethyl sulphoxide (DMSO) control. The percentage of (A) interferon γ (IFNγ)⁺ CD4⁺ and (B) IFNγ⁺ CD8⁺ T cells was measured by flow cytometry. Dotted lines represent the limit of detection following DMSO background subtraction (IFNγ of CD4⁺ = 0.001, IFNγ of CD8⁺ = 0.001). (C) The proportion of IFNγ producing IL‐2 and TNF‐α CD4⁺ and CD8⁺ T cells post vaccination. (D) The phenotype (by CCR7 and CD45RA) of IFNγ responses for T effector memory (TEM), central memory (TCM), terminal effector memory (TeEM) or naïve (TN) CD4⁺ and CD8⁺ T cells post vaccination. Bars represent the mean values, and error bars represent SD. Statistical significance was determined by paired t‐test between pre‐ versus post‐vaccination timepoint samples, and Kruskal–Wallis test for multiple comparisons between vaccines, and COVID‐19 patients. *p < 0.05; **p < 0.01; ***p < 0.001