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Table 2 Comparison of different prime-boost immunization strategies on immunogenicity in included studies

From: Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review

Comparisona

First author

RBD Abb

Spike protein Abb

Neutralizing Abb

T cell response and othersb

Conclusion

ChAd/BNT vs BNT/BNT

Louise Benning [21]

NS in MFI values

Higher MFI of full spike protein (24,243 vs 23,849), S1 protein (19,332 vs 16,955), and S2 protein (13,138 vs 9696) values

Comparable anti-S1 IgG levels (116.2 to 145.5) dimensionless index

NS in inhibition of RBD-ACE2 binding (96.8% vs 97.0%)

NR

ChAd/BNT superior to BNT/BNT in spike protein Ab, while comparable in RBD and neutralizing Ab

ChAd/BNT vs BNT/BNT

Joana Barros-Martins [12]

NR

NS in Anti-S IgG (625.7 vs 303.2 RU/ml by quantitative ELISA) and IgA (3.76 vs 2.56 ratio)

NR

NR

ChAd/BNT comparable to BNT/BNT in Anti-S IgG and IgA

ChAd/BNT vs BNT/BNT

Xinxue Liu [14]

NR

NS in Anti-S IgG levels (12,995 vs 13,938 ELU/mL by ELISA)

NS in PNA NT50 (515 vs 574)

NR

ChAd/BNT comparable to BNT/BNT in Anti-S IgG levels and PNA NT50

ChAd/BNT vs BNT/BNT

Alexandre Vallée [28]

NR

NS in S protein IgG levels (7268.6 vs 10,734.9 RLU by CMIA)

NR

NR

ChAd/BNT comparable to BNT/BNT in S protein IgG

ChAd/BNT vs BNT/BNT

David Hillus [13]

NS in anti-RBD IgG (5.6 vs 5.4S/Co by solid phase immunoassay)

NS in anti-full S and anti-S1 IgG

Higher Anti-S1 IgG avidity index (93.6% vs 73.9%)

NS in ACE2–RBD binding inhibition (97.1% to 96.6%)

Higher serum neutralising activity (ID50 against to alpha variant 956.6 vs 369.2, ID50 against to beta variant 417.1 vs 72.4)

Higher S-specific T-cell responses (IFN-γ: 4762 vs 2026 mIU/mL)

ChAd/BNT superior to BNT/BNT in serum neutralising activity and S-specific T-cell responses; Comparable in anti-RBD IgG, anti-full S, anti-S1 IgG and anti-S1 IgG avidity

ChAd/BNT vs BNT/BNT

Dorit Fabricius [15]

NR

NR

Higher neutralization capacities against wildtype RBD and B.1.1.7 variant (82% to 63%)

Higher IFN-γ secretion

ChAd/BNT superior to BNT/BNT in neutralization capacities and T cells responses

ChAd/BNT vs BNT/BNT

Matthias Tenbusch [27]

NR

NR

Higher surrogate neutralisation activity (IC50: 3377 to 1789AU/mL)

NR

ChAd/BNT superior to BNT/BNT in neutralisation Ab

ChAd/BNT vs BNT/BNT

Swantje I. Hammerschmidt [23]

NR

NR

Lower reciprocal titers of neutralizing against Delta (180 to 540)

NR

ChAd/BNT inferior BNT/BNT in neutralisation Ab

ChAd/(BNT or mRNA-1273) vs (BNT or mRNA-1273)/(BNT or mRNA-1273)

Tina Schmidt [26]

NS in IgG to RBD of S protein (3630 vs 4932 BAU/mL by ELISA)

NR

Higher in inhibition of ACE2-S1 RBD (100.07% to 99.68%)

Higher percentages of spike-specific IFN-γ-producing CD8 T cells levels (0.28% to 0.06%)

NS in CD4 T cells levels (0.17% to 0.16%)

ChAd/BNT superior to mRNA-1273 in neutralizing Ab and CD8 T cells levels, while comparable in RBD Ab and CD4 T cells levels

ChAd/mRNA-1273 vs BNT/BNT

Dorit Fabricius [15]

NR

NR

Higher neutralization capacities against wildtype RBD and B.1.351 variant (85% to 59%), B.1.1.7 variant (87% to 63%)

NR

ChAd/mRNA-1273 superior to BNT/BNT in neutralization capacities

Comparison

First Author

RBD Ab

Spike protein Ab

Neutralizing Ab

T cell response and others

Conclusion

ChAd/BNT vs BNT/BNT

Rudiger Gross [22]

NR

8.1-fold higher quantified cumulative anti-spike-IgM and IgG concentrations (8815 vs 1086 U/ml)

3.9-fold higher neutralizing activity correlated with IgG or IgM/G titres (2744 vs 709)

Levels of spike-specific CD8 + T cells producing IL-2 in agreement with BNT/BNT

ChAd/BNT superior to BNT/BNT in spike IgM and IgG and neutralizing activity, while comparable in T cell response

ChAd/BNT vs BNT/BNT

Bruno Pozzetto [25]

NS in positivity rate of RBD IgG (both 100%)

NS in positivity rate of spike S1-specific IgG (both 100%); NS in S1-specific IgA levels (37.4 vs 46.7 ng/ml)

Higher neutralizing efficacy (99% vs 62%); 2.3-fold to 3.6-fold higher serum neutralizing antibody titres against different variants

Two fold higher in frequency of RBD-binding mBCs; higher in IgDCD27+ (67% vs 47%); lower in IgG-switched mBCs (48% vs 62%); three times higher in proportions of CD21CD11c+ subset; higher in proportions of frequencies of activated RBD-specific mBCs; similar in whole-blood IFNγ (0.43 vs 0.33 UI/ml)

ChAd/BNT superior to BNT/BNT in neutralizing efficacy, T cell response, and B cell activation

ChAd/BNT vs BNT/BNT

Samantha J Westrop [29]

NR

NS in anti-S antibody level (6233 vs 5377), adjusted GMR:1.11

NR

NR

ChAd/BNT inferior to BNT/BNT in anti-S IgG levels

ChAd/mRNA-1273 vs mRNA-1273/mRNA-1273

Swantje I. Hammerschmidt [24]

NR

NR

Lower in neutralizing antibodies against the Delta variant (540 vs 1620)

NR

ChAd/mRNA-1273 inferior to mRNA-1273/mRNA-1273 in neutralizing antibodies against Delta variant

ChAd/BNT vs ChAd/ChAd

Louise Benning [21]

NR

Higher anti-S1 IgG levels (116.2 vs 13.1) by dimensionless index (CLIA)

Higher (96.8% vs 93.5%) in inhibition of RBD-ACE2 binding

NR

ChAd/BNT superior to ChAd/ChAd in S1 protein and neutralizing Ab

ChAd/BNT vs ChAd/ChAd

Joana Barros-Martins [12]

NR

Higher Anti-S IgG (625.7 vs 160.9 RU/ml by quantitative ELISA) and IgA (3.76 vs 0.87 ratio)

Higher reciprocal titers of neutralizing antibodies against Wuhan (4840 vs 540), B.1.1.7 (540 vs 20), P.1 (60 vs 0) and B.1.351 (60 vs 0) variants

Higher in spike-specific CD4 + and CD8 + T cells

Higher in IFN-γ concentration

NS in spike-specific memory B cells

NS in TNF-α concentration

ChAd/BNT superior to ChAd/ChAd in S protein, neutralizing Ab and T cellular response, while comparable in memory B cells and TNF-α

ChAd/BNT vs ChAd/ChAd

Xinxue Liu [14]

NR

Higher in Anti-S IgG levels (12,995 vs 1387 ELU/mL by ELISA), GMR: 9.3

Higher in MNA NT50 titer (1269 vs 210), PNA NT50 titer (515 vs 61), GMR: 6.4 for MNA NT50 and 8.5 for PNA NT50

Higher in T-cell ELISpot, SFC per million PBMCs (184 vs 48), GMR: 3.9

ChAd/BNT superior to ChAd/ChAd in anti-S IgG levels, MNA NT50, PNA NT50, and cellular responses

ChAd/BNT vs ChAd/ChAd

David Hillus [13]

Similar in anti-RBD IgG (5.6 vs 4.9 S/Co by solid phase immunoassay)

Higher Anti-S1 IgG avidity index (93.6% vs 71.7%)

NS in anti-full S and anti-S1 IgG

Higher ACE2–RBD binding inhibition (97.1% vs 92.4%)

Higher serum neutralising activity (ID50 against to alpha variant 956.6 vs 212.5, ID50 against to beta variant 417.1 vs 48.5)

Higher S-specific T-cell responses (IFN-γ:4762 vs 1061 mIU/mL)

ChAd/BNT superior to ChAd/ChAd in anti-S1 IgG avidity, serum neutralising activity and S-specific T-cell responses, while comparable in anti-RBD IgG, anti-full S and anti-S1 IgG

Comparison

First Author

RBD Ab

Spike protein Ab

Neutralizing Ab

T cell response and others

Conclusion

ChAd/BNT vs ChAd/ChAd

Dorit Fabricius [15]

NR

Higher Anti-S1 IgG and IgA

Higher neutralization capacities against wildtype RBD and B.1.1.7 variant (82% vs 48%), B.1.351 variant (70% vs 57%), P.1 variant (55% vs 15%)

Higher IFN-γ secretion

ChAd/BNT superior to ChAd/ChAd T in neutralization capacities and T cells responses

ChAd/BNT vs ChAd/ChAd

Matthias Tenbusch [27]

NR

NR

Higher surrogate neutralisation activity (IC50: 3377 vs 106 AU/mL)

NR

ChAd/BNT superior to ChAd/ChAd in neutralisation Ab

ChAd/BNT vs ChAd/ChAd

Swantje I. Hammerschmidt [23]

NR

NR

Higher reciprocal titers of neutralizing against Delta (180 vs 20)

NR

ChAd/BNT superior to ChAd/ChAd in neutralisation Ab

ChAd/BNT or mRNA-1273 vs ChAd/ChAd

Tina Schmidt [26]

Higher IgG levels to RBD of S protein (3630 vs 404 BAU/mL by ELISA)

NR

Higher in inhibition of ACE2-S1 RBD (100.07% vs 83.37%)

Higher percentages of spike-specific IFN-γ-producing CD8 T cells levels (0.28% vs 0.04%) and CD4 T cells levels (0.17% vs 0.04%)

ChAd/BNT or mRNA-1273 superior to ChAd/ChAd in RBD Ab, neutralizing Ab, CD4 T cells, and CD8 T cells levels

ChAd/BNT vs ChAd/ChAd

Samantha J Westrop [29]

NR

Higher in anti-S antibody level (6233 vs862), adjusted GMR:6.29

NR

NR

ChAd/BNT superior to ChAd/ChAd in anti-S antibody

ChAd/mRNA-1273 vs ChAd/ChAd

Swantje I. Hammerschmidt [24]

NR

NR

Higher in neutralizing antibodies against the Delta variant(540 vs 20)

NR

ChAd/mRNA-1273 superior to ChAd/ChAd in neutralizing antibodies against Delta variant

BNT/ChAd vs BNT/BNT

Xinxue Liu [14]

NR

Lower anti-S IgG levels (7133 vs 13,938 ELU/mL by ELISA), GMR:0.51

Lower PNA NT50 titer (383 vs 574), GMR:0.67

NS in SFC per million PBMCs, T-cell ELISpot (90 vs 81), GMR: 1.2

BNT/ChAd inferior to BNT/BNT in anti-S IgG levels and PNA NT50, while comparable in T cellular responses

BNT/ChAd vs BNT/BNT

Samantha J Westrop [29]

NR

NS in anti-S antibody level (4776 vs 5377), adjusted GMR:0.80

NR

NR

BNT/ChAd inferior to BNT/BNT in anti-S IgG levels

BNT/ChAd vs ChAd/ChAd

Xinxue Liu [14]

NR

Higher anti-S IgG levels (7133 vs 1387ELU/mL by ELISA)

Higher PNA NT50 titer (383 vs 61)

NR

BNT/ChAd superior to ChAd/ChAd in anti-S IgG levels and PNA NT50

BNT/ChAd vs ChAd/ChAd

Samantha J Westrop [29]

NR

Higher in anti-S antibody level (4776 vs862), adjusted GMR:4.55

NR

NR

BNT/ChAd superior to ChAd/ChAd in anti-S antibody

  1. Ab antibody, BNT BNT162b2 vaccine, Pfizer–BioNTech, ChAd ChAdOx1 nCoV-19 vaccine, AstraZeneca, NR not reported, MFI mean fluorescence intensity, RBD receptor-binding domain, ACE2 angiotensin-converting enzyme 2, PNA pseudotype virus neutralization assay, NT50 50% neutralising antibody titre, CMIA chemiluminescent microparticle immunoassay, ID50 50% inhibitory dilutions, IFN-γ interferon-γ, IC50 inhibitory 50% concentration, ELISA enzyme-linked immunosorbent assay, GMR geometric mean ratio, NT50 50% neutralising antibody titre, SFC spot-forming units, PBMC peripheral blood mononuclear cell, mBCs memory B cells
  2. aStudies in the table were arranged by the types of prime-boost immunization strategies. Some studies may include more than one type of prime-boost immunization strategy or more than one comparative group, so these studies were presented in more than one row
  3. bAll the comparisons in the table indicate the value of heterologous prime-boost vaccination vs that of homologous prime-boost vaccination