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) | NA | Fair |
| 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) | NA | Fair |
| 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) | NA | Good |
| Capuano et al, (Italy)30 | 57 (26, 31) | BNT162b2 (mRNA) | Serum anti-S IgG (CLIA, DiaSorin) | NA | Good |
| Disanto et al, (Switzerland)21 | 116 (116, 0) | BNT162b2 (mRNA) mRNA-1273 (mRNA) | Serum anti-RBD IgG (CMIA, Abbot) | NA | Good |
| Etemadifar et al, (Iran)15 | 358 (144, 214) | BBIBP-CorV (Inactivated) | Serum anti-S IgG (ELISA, Pishtazteb) | NA | Good |
| 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) | NA | Fair |
| Giossi et al, (Italy)12 | 312 (39, 273) | BNT162b2 (mRNA) | Serum anti-RBD IgG (CMIA, Abbot) | NA | Fair |
| 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) | NA | Fair |
| 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) | NA | Good |
| Ozakbas et al, (Turkey)16 | 591 (547, 44) | BNT162b2 (mRNA) CoronaVac (Inactivated) | Serum anti-RBD IgG (CMIA, Abbot) | NA | Good |
| Pitzalis et al, (Italy)22 | 975 (912, 63) | BNT162b2 (mRNA) | Serum anti-RBD IgG (ECLIA, Roche) | NA | Fair |
| 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) | NA | Good |
| 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) | NA | Fair |
| Van Kempen et al, (Netherlands)80 | 87 (87, 0) | mRNA-1273 (mRNA) | Serum anti-RBD IgG (ELISA, NR) | NA | Fair |
| Studies with no comparators | |||||
| Guerrieri et al, (Italy)81 | 32 (32, 0) | BNT162b2 (mRNA) mRNA-1273 (mRNA) | Various assays | NA | NA |
| Novak et al, (Denmark, USA)82 | 60 (60, 0) | mRNA vaccines | Serum anti-RBD IgG (CMIA, Abbot) | NA | NA |
| Grothe et al, (Germany)35 | 38 (38, 0) | BNT162b2 (mRNA) mRNA-1273 (mRNA) ChAdOx1 (AV) | Serum anti-S IgG (CLIA, DiaSorin) | NA | NA |
*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: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). 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.