Table 1.

Characteristics of trials included in the meta-analysis (comparison: MVA vs. comparator).

Study ID	Comparison	Study Population	MVA-Way of Administration	MVA-Dose	MVA-Formulation	Duration of Follow-Up (Longest)	No Randomized	Age	Previously Vaccinated	Primary Outcome
Frey 2007 [20]	MVA (5 arms) vs. placebo	Healthy, vaccinia-naive	Arms 1-3: SC 2 MVA doses + Dryvax Arm 4: placebo Arm 5: SC 2 MVA doses + placebo Arm 6: IM 2 MVA doses + Dryvax	Arm 1: 2 × 107 TCID50 Arm 2: 5 × 107 TCID50Arm 3: 1 × 108 TCID50 Arm 5: 1 × 108 TCID50 Arm 6: 1 × 108 TCID50	Lyophilized	140 days	90	18–32	None	Adverse events, cellular and humoral immune responses, compare routes of administration (at days 14, 28, 42, 56, 112 and 140)
Greenberg 2016 [15]	MVA vs. placebo *	Vaccinia-experienced	SC	Arm 1: 1 × 108 TCID50, second dose at 4 weeks Arm 2: placebo at day 0, MVA 1 × 108 TCID50 at 4 w	Liquid	Short 8–10 w; long 6 months	120	56–80	100%	Safety in a vaccinia-experienced population after administration of either one or two doses of MVA
Overton 2018 [21]	MVA (3 different lots) vs. placebo	Healthy, vaccinia-naive	SC	1 × 108 TCID50 Second dose at 4 weeks	Liquid	26 w after second dose	4005	18–40	None	Geometric Mean Titers (by PRNT) 2 w after second vaccination
Parrino 2007 naïve [16]	MVA (1, 2, or 3 doses) vs. placeboDryvax at 12 w for all	Healthy, vaccinia-naive	IM	1 × 108 TCID50 Either 1, 2 or 3 doses at week 0, 4, 12	Liquid	24 weeks after the last MVA/placebo dose	76	18–32	None	Safety and clinical protection against vaccinia (Dryvax®) challenge
Parrino 2007 immune [16]	MVA (1 or 2 doses) vs. placebo Dryvax at 12 w for all	Healthy, vaccinia-immune	IM	1 × 108 TCID50 Either 1 or 2 doses at week 0, 4	Liquid	24 weeks after the last MVA/placebo dose	75	18–61	100%	Safety and clinical protection against vaccinia (Dryvax®) challenge
Pittman 2019 [14]	MVA vs. ACAM2000	Healthy persons	SC, over deltoid muscle	1 × 108 TCID50 Second MVA dose at week 4; then ACAM2000 dose at week 8	Liquid	6 months after last vaccination	440	18–42	None	Geometric mean titers of neutralizing antibodies at 4 (ACAM) and 6 (MVA) weeks
Walsh 2013 [17]	MVA (2 arms of different doses) vs. placebo	HSCT recipients (at least 2 years after transplant)	SC	Arm 1: 1 × 107 TCID50 Arm 2: 1 × 108 TCID50 Second MVA dose at week 4 for both arms	Liquid	Short: 56 days; long: 180 d	24	18–60	None	Safety and reactogenicity
Zitzmann- Roth 2015 (and a following publication–Ilchmann 2023) [19,22]	MVA vs. placebo (3 arms–MVA 2 doses, MVA one dose, placebo)	Healthy, vaccinia-naive	SC	1 × 108 TCID50 Arm 1: second MVA dose at week 4 Arm 2: second dose of placebo at week 4 Arm 3: 2 placebo doses, 0, 4 w	Liquid	Short—28–35 d after 2nd dose; long—6 m	545	18–55	None	Zitzmann-Roth: Safety–ECG changes and cardiac symptoms. Ilchmann: Geometric mean titers of neutralizing antibodies

NC—not specified; SC—subcutaneous; HSCT—hematopoietic stem cell transplantation; PRNT—plaque reduction neutralization test. * The comparison of MVA vs. placebo was for 4 weeks, during which the placebo group received an MVA dose. For studies using Dryvax, this vaccine was administered at a later stage, and all reported outcomes collected for this meta-analysis were prior to Dryvax administration.