Table 1

Characteristics of included studies

Study (location)Sample size (pwMS, HC)Vaccine (platform)B-cell assay (method, manufacturer)T-cell assay (method, manufacturer)Study quality*
Achiron et al, (Israel)
19 77 78
503 (414, 89)BNT162b2 (mRNA)Serum anti-S1 IgG (ELISA, EUROIMMUN)
PBMC S-induced IgG-secreting B-cells (FluoroSpot, Mabtech)
PBMC S-induced IFN-g-, IL-2-positive T-cells (FluoroSpot, Mabtech)Good
Ali et al, (USA)58 53 (46,† 7)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum Anti-RBD IgG (CLIA, Siemens)NAFair
Apostolidis et al, (USA)39 30 (20, 10)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum anti-S IgG (ELISA, NA)
Serum anti-RBD IgG (ELISA, NA)
PBMC S-induced IgG-secreting B-cells (Cell Probe, NA)
PBMC S-induced activation marker-positive T-cells (AIM, NA)Fair
Bigaut et al, (France)9 28 (28, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum anti-RBD IgG (CMIA, Abbot; ECLIA, Roche)NAFair
Brill et al, (Israel)40 112 (72, 40)BNT162b2 (mRNA)Serum anti-S IgG (CLIA, DiaSorin)
Serum anti-RBD IgG (CMIA, Abbot)
PBMC S/N-induced IFN-g-positive T-cells (ELISpot, Oxford Immunotec)Fair
Capone et al, (Italy)10 140 (140, 0)BNT162b2 (mRNA)Serum anti-RBD IgG (CMIA, Abbot)NAGood
Capuano et al, (Italy)30 57 (26, 31)BNT162b2 (mRNA)Serum anti-S IgG (CLIA, DiaSorin)NAGood
Disanto et al, (Switzerland)21 116 (116, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum anti-RBD IgG (CMIA, Abbot)NAGood
Etemadifar et al, (Iran)15 358 (144, 214)BBIBP-CorV (Inactivated)Serum anti-S IgG (ELISA, Pishtazteb)NAGood
Gadani et al, (USA)11 101 (101, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)
Ad26.COV2.S (AV)
Serum anti-S1 IgG (ELISA, EUROIMMUN)PBMC S-induced IFN-g-positive T-cells (FluoroSpot, Mabtech)Fair
Gallo et al, (Italy)79 59 (4, 55)BNT162b2 (mRNA)Serum anti-S IgG (CLIA, DiaSorin)NAFair
Giossi et al, (Italy)12 312 (39, 273)BNT162b2 (mRNA)Serum anti-RBD IgG (CMIA, Abbot)NAFair
Katz et al, (USA)43 48 (48, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)
Ad26.COV2.S (AV)
Serum anti-RBD IgG (ECLIA, Roche)Rearranged TCR gene sequences (M-PCR, Adaptive Biotechnologies)Fair
König et al, (Norway)23 1155 (528, 627)BNT162b2 (mRNA) mRNA-1273 (mRNA)
ChAdOx1 (AV)
PBMC S-induced IgG-secreting B-cells (BBFCA, NA)
PBMC RBD-induced IgG-secreting B-cells (BBFCA, NA)
Madelon et al, (Switzerland)41 48 (26, 22)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum anti-RBD IgG (ECLIA, Roche)PBMC S-induced activation marker-positive T-cells (AIM, NA)Fair
Maniscalco et al, (Italy)13 149 (125, 24)BNT162b2 (mRNA)Serum anti-RBD IgG (ECLIA, Roche)NAGood
Ozakbas et al, (Turkey)16 591 (547, 44)BNT162b2 (mRNA)
CoronaVac (Inactivated)
Serum anti-RBD IgG (CMIA, Abbot)NAGood
Pitzalis et al, (Italy)22 975 (912, 63)BNT162b2 (mRNA)Serum anti-RBD IgG (ECLIA, Roche)NAFair
Pompsch et al, (Germany)42 30 (10, 20)BNT162b2 (mRNA)Serum anti-S1 IgG (ELISA, EUROIMMUN)S/N/M-induced IFN-g-positive T-cells (ELISpot, Miltenyi Biotec)Fair
Sabatino et al, (USA)17 80 (67, 13)BNT162b2 (mRNA) mRNA-1273 (mRNA)
Ad26.COV2.S (AV)
PBMC S-induced IgG-secreting B-cells (BBFCA, NA)
PBMC RBD-induced IgG-secreting B-cells (BBFCA, NA)
PBMC S-induced activated T-cells (AIM; ICS; pMHC, NA)Fair
Sormani et al, (Italy)20 57 780 (780, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum anti-RBD IgG (ECLIA, Roche)NAGood
Tallantyre et al, (UK)24 473 (473, 0)BNT162b2 (mRNA)
ChAdOx1 (AV)
Ad26.COV2.S (AV)
Serum anti-RBD IgG (ELISA, Kantaro Biosciences; GloBody, NA)PBMC S/N/M-induced IFN-g-positive T-cells (ELISpot, ImmunoServ Ltd.)Fair
Tortorella et al, (Italy)14 186 (108, 78)BNT162b2 (mRNA) mRNA-1273 (mRNA)Serum anti-RBD IgG (NR)
Neutralising antibodies (MNA, NA)
Whole blood S-induced IFN-g (ELISA, ProteinSimple)Fair
Türkoğlu et al, (Turkey)25 59 (34, 25)CoronaVac (Inactivated)Serum anti-S1 IgG (ELISA, EUROIMMUN)NAFair
Van Kempen et al, (Netherlands)80 87 (87, 0)mRNA-1273 (mRNA)Serum anti-RBD IgG (ELISA, NR)NAFair
Studies with no comparators
Guerrieri et al, (Italy)81 32 (32, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)Various assaysNANA
Novak et al, (Denmark, USA)82 60 (60, 0)mRNA vaccinesSerum anti-RBD IgG (CMIA, Abbot)NANA
Grothe et al, (Germany)35 38 (38, 0)BNT162b2 (mRNA) mRNA-1273 (mRNA)
ChAdOx1 (AV)
Serum anti-S IgG (CLIA, DiaSorin)NANA
  • *Assessed with National Institutes of Health quality assessment tools (The rationale of judgements are presented in an online supplemental file 2; The used criteria are available at: Good means least risk of bias; Fair, low risk of bias and Poor, moderate/high risk of bias.

  • †Including two participants with neuromyelitis optica and two with optic neuritis.

  • AIM, activation-induced marker; AV, adenoviral vector; BBFCA, bead-based flowcytometry assay; CLIA, chemiluminescent immunoassay; CMIA, chemiluminescence microparticle immunoassay; ECLIA, electrochemiluminescence immunoassay; HC, healthy controls; ICS, intracellular cytokine staining; IFN-g, interferon-gamma; IL, interleukin; M, membrane protein; MNA, microneutralisation assay; M-PCR, multiplex PCR; mRNA, messenger RNA; N, nucleocapsid protein; NA, not applicable; NR, not reported; PBMC, peripheral blood mononuclear cells; pMHC, peptide major histocompatibility complex; pwMS, people with multiple sclerosis; RBD, receptor-binding domain; S, spike protein.