Table 2.
Immunogenicity of heterologous regimens including vector-based and mRNA-based vaccines (ChAd/BNT or ChAd/mRNA-1273).
| Vaccine platform | Studies | Outcomes | ChAd/BNT (Mean (95% CI)) | ChAd/ChAd (Mean (95% CI)) | BNT/BNT (Mean (95% CI)) | Major results |
|---|---|---|---|---|---|---|
| ChAd and BNT | Borobia[22] | Spike protein Ab | 3684.87 BAU/ml (3851.58–4920.85),Ratio was 36.41-fold increase from baseline | ChAd prime only: 101.2 BAU/ml (82.45–124.22) | NA | Heterologous vaccination induced robust response |
| RBD Ab | The number was higher compared with ChAd prime: 7756.68 BAU/ml (7371.53–8161.96) | 99.84 BAU/ml (76.93–129.59) | ||||
| Neutralizing Ab | GMT: increased 45-times, from 41.84 to 1905.69 (1625.65–2233.98) | 41.81 (27.18–64.32) | ||||
| T cell response | IFN-γ significantly increased with GMT: 521.22 pg/ml (422.44–643.09) | 122.67 pg/ml (88.55–169.95) | ||||
| Liu[28] | Spike protein Ab | 12,906 ELU/ml (11,404–14,604) | 1392 ELU/ml (1188–1630) | 14,080 ELU/ml (12,491–15,871) | The higher immunogenicity of mixing vaccination compared with ChAd/ChAd was demonstrated | |
| Neutralizing Ab | Pseudotype virus neutralizing Ab (NT50): 515 (430–617) | 61(50–73) | 574 (475–694) | |||
| T cell response | SFC per million PBMCs: 184 (152–223) | 48 (37–61) | 80 (63–101) | |||
| Hillus[23] | Serum Ab avidity | 100% (88.6–100) | 83% (66.4–92.7) | 90% (74.4–96.5) | The heterologous improved immunogenicity compared with homologous ChAd/ChAd | |
| RDB Ab | 5.6 S/Co (5.1–6.1) | 4.9 S/Co (4.3–5.6) | 5.4 S/Co (4.8–5.9) | |||
| Neutralizing Ab | Reactive neutralizing Ab: 100% (96.1–100) | 88% (71.9–95.0) | 99% (94.6–99.5) | |||
| T cell response | INF-γ concentration: 4762 mIU/ml (IQR: 2723–8403) | 1061 mIU/ml (IQR: 599–2274) | 2026 mIU/ml (IQR 1459–4621) | |||
| Groβ[24] | Spike protein Ab | Median IgG titers increased 135-fold (63.9 U/ ml, 4.27–2005→8815 U/ml, 1206–19,046) | NA | NA | The heterologous ChAd/BNT was potent humoral immune response and elicits T cell reactivity | |
| Neutralizing Ab | Median ACE2 neutralization increased after BNT booster (62%, 32–95–>98%, 89–98) | |||||
| T cell response | 100% participants developed CD4 +T cells and 89% produced CD8 + T cells | |||||
| Barros[30] | Spike protein Ab | Ab IgG: 625.7 RU/mlAb IgA: 3.76 RU/ml | Ab IgG: 160.9 RU/mlAb IgA: 0.87 RU/ml | Ab IgG: 574.1 RU/mlAb IgA: 5.06 RU/ml | Mixing vaccination provided potent higher immune response to ChAd/ChAd group. Boosting with BNT induced higher frequency of T cells response | |
| T cell response | A significant higher T cell response in ChAd/ BNT group | |||||
| B cell response | Similar extent in expansion of spike-specific memory B in all groups | |||||
| Behrens[31] | Spike protein Ab | 611.o RU/ml (SD: 104.5) | 171.9 RU/ml (SD: 121.8) | NA | Study supported for heterologous boost vaccination of individuals with completed homologous ChAd vaccination | |
| Benning[32] | Spike protein Ab | 116.2 9IQR 61.84–170) | 13.09 (IQR 7.03–29.02) | 145.5 (IQR 100–291.1) | Heterologous induced strong and broad humoral response | |
| Neutralizing Ab | Percent of inhibition 96.8 (IQR 96.7–96.9) | 93.5 (88.6–96.7) | 97.0 (96.1–98.0) | |||
| Dimeglio[34] | Neutralizing Ab | 95.4% | 63.6% | 68.2% | ChAd/BNT heteroglous regimen provided a stronger Ab response than either of the homologous regimens | |
| Valiée[21] | Spike protein Ab | 7268.6 (6501.3–8128.3) | NA | 10,734.9 (9141.1–12,589.3) | Applying heterologous second dose of BNT was associated with decrease of Ab response levels compared to homologous BNT vaccination | |
| ChAd, mRNA, BNT | ChAd/mRNA | mRNA/mRNA | ChAd/ChAd | |||
| In these two studies, the mRNA was mRNA 1273-vaccine from Moderna company | Fabricius[35] | Neutralizing Ab | ‘ > 85% participants exhibited stronger neutralizing capacity | ‘> 90% vaccinated individuals exhibited no or medium level neutralization capacity | Heterologus vaccination booster regimens with mRNA could allow enhanced protection against SARS-CoV-2 | |
| T cell response | Peak IFN-γ secretion was significant stronger | |||||
| Normark[29] | Spike protein Ab | 115 time as high as. 128,108 | NA | 4320 | Potent induction of SARS-CoV-2 immune response had trend to be higher in heterologous group | |
| RBD Ab | 125 times as high as, 41,680 | 1224 | ||||
| Neutralizing Ab | Reciprocal serum neutralization titer 20 times as high as | NA | ||||
| In these two studies, the mRNA was either BNT and mRNA1273from Moderna | Schmidt cellular[27] | Humoral response | In transplant recipients, the heterologous regimen led to significant induction in IgG level and neutralizing activity | |||
| T cell response | CD4 T cell levels was reported a significant increase in mixing boosting compared to mRNA boosting | |||||
| Schmidt[33] | Spike protein Ab | 3630 BAU/ml (IQR 3721) | 4932 (IQR 4239) | 404 (IQR 510) | Heterologous strategy led to a strong induction of both antibodies and T cells and approximately tenfold higher than hom0ologous vector vaccination | |
| Neutralizing Ab | Majority of individuals had 100% inhibitory activity | This number was lower | ||||
| T cell response | Median % was 0.17 (IQR 0.13%) | 0.16 (IQR 0.19%) | 0.04 (IQR 0.04%) | |||
cell; Ab: antibody; RBD: receptor binding domain; IQR: presented as median; SD: standard deviation; GMT: Geometric mean titerss; SFC: spot-forming units; PMBC: peripheral blood mononuclear; NA: Not available; CI: confidence interval; mRNA: messenger RNA; mRNA1273: Vaccine from Moderna company; ChAd: Astrazeneca, vector (Covisheld) vaccine; BNT: Pfizer mRNA vaccine