Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity

Abstract

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

Keywords: BNT162b2; COVID-19; CoronaVac; inborn errors of immunity; vaccine.

Figure 1

Adverse reactions (ARs) and antipyretic use reported 7 days after each dose by vaccine brand. B, BB, and BBB refer to 1, 2, and 3 doses of BNT162b2 while C, CC, and CCC refer to 1, 2, and 3 doses of CoronaVac. Stacked bar chart shows ARs by maximal severity in different colors. Severity was self-graded by participants, according to whether the AR affected daily activity (mild – tolerable, not affecting daily activities, moderate - performance of some daily activities affected, or severe - performance of some daily activities prevented), or for swelling, erythema and induration at injection site, the diameter affected (mild – 2-5 cm, moderate – 5-10 cm, severe – above 10 cm), or for fever, the body temperature (mild – 38.0-38.4°C, moderate – 38.5-38.9°C, severe – 39.0 °C or above).

Figure 2

Wild-type (WT) Spike-receptor binding domain (S-RBD) IgG and surrogate virus neutralization test (sVNT) results after COVID-19 vaccination by disease category. (A) and (B) show S-RBD IgG and sVNT results respectively in five disease categories (combined, humoral, innate, dysregulation and phagocytic) after 2 doses, while C and D show S-RBD and sVNT results after 3 doses. Geometric means (GM) are shown with centre lines and stated above each column. Limits of detection and quantification (LOD and LOQ) were drawn as grey lines, and the y-axis shows the range of the assays. Number of analyzed available samples (n) are also stated above each column. A and B included 2 patients (one each in combined and innate) who received first 2 doses intradermally and their datapoints were shown as darkened squares. (C) and (D) also included 4 patients (1 each in combined, humoral, innate and dysregulation) who received their third dose intradermally and their datapoints were also shown as darkened squares. .

Figure 3

Wild-type (WT) S peptide pool-specific interferon-γ (IFN-γ)⁺ CD4⁺ and CD8⁺ T cells after COVID-19 vaccination by disease category. (A) and (B) show S-specific IFN-γ⁺ CD4⁺ and CD8⁺ results respectively in five disease categories (combined, humoral, innate, dysregulation and phagocytic) after 2 doses, while C and D show S-specific IFN-γ⁺ CD4⁺ and CD8⁺ results after 3 doses. Geometric means (GM) are shown with center lines and stated above each column. Cut-offs were drawn as grey lines. Number of analyzed available samples (n) are also stated above each column. A and B included 1 patient (in combined) who received first 2 doses intradermally and their datapoints were shown as darkened squares. (C) and (D) also included 4 patients (1 each in combined, humoral, innate and dysregulation) who received their third dose intradermally and their datapoints were also shown as darkened squares.

Figure 4

Longitudinal analysis of (A), wild-type (WT) Spike-receptor binding domain (S-RBD) IgG, (B), WT surrogate virus neutralization test (sVNT) results, and (C), Omicron BA.1 sVNT by vaccine brand. Geometric means (GM) are shown with center lines and stated above each column. Limits of detection and quantification (LOD and LOQ) and cut-offs were drawn as grey lines. Data from participants receiving intradermal vaccination were shown as darkened squares beginning at their initial intradermal dose. Data from the same participant were analyzed longitudinally by paired t test after natural logarithmic transformation, and the P values are denoted by asterisks (*, P<0.05; **, P<0.01; ns, not significant).

Figure 5

Longitudinal analysis of wild-type (WT) S and S, N and M protein peptide pool-specific interferon-γ (IFN-γ)⁺ CD4⁺ and CD8⁺ T cells by vaccine brand and route. S-specific IFN-γ⁺ CD4⁺ and CD8⁺ T cell responses are shown in (A, B) respectively for both BNT162b2 and CoronaVac recipients, while added SNM-specific IFN-γ⁺ CD4⁺ and CD8⁺ T cell responses are shown in (C, D) for CoronaVac recipients. Samples from the same patient were paired between baseline and post-dose 2 timepoints as well as post-dose 2 and post-dose 3 timepoints, and compared with paired t test after natural logarithmic transformation with p-values denoted (**, P<0.01; ns, not significant).