Table 1.

Second-generation vaccinia-based smallpox vaccines.

Vaccine	Subjects Enrolled 1	Findings	AEs/SAEs	Reference
ACAM1000 (Acambis)	60 VACV-naïve healthy volunteers	100% take and seroconversion rate	No SAEs; no difference in local reactogenicity between ACAM1000 & Dryvax	[49,57]
	70 VACV-naïve healthy volunteers	100% take rate, 94% seroconversion rate	No SAEs; local reactogenicity common; other AEs mild
ACAM2000	100 VACV-naïve healthy volunteers	99% take rate, 96% seroconversion rate	Local reactogenicity common; 1 SAE (new-onset seizure)	[47,57,59,60]
	90 VACV-naïve healthy volunteers	100% take rate, 96% seroconversion in ACAM2000 group	Local reactogenicity common; 2 SAEs (transient EKG changes in an ACAM2000 vaccinee, transient neutropenia in ACAM1000 vaccinee)
	353 VACV-naïve healthy volunteers	100% take rate at full dose, <90% take rate when diluted; dose-response trend for antibodies	Local reactogenicity slightly less with ACAM2000 than Dryvax; 1 case of myocarditis in ACAM2000 group
	357 VACV-experienced healthy volunteers	88% take rate at full dose, greatly decreased take rate when diluted; dose-response trend for antibodies	Not reported
	1162 VACV-naïve healthy volunteers	96% take rate, not inferior to Dryvax	No differences in AEs between ACAM2000 and Dryvax; 5 cases of myopericarditis with ACAM2000 and 3 cases with Dryvax
	1819 VACV-experienced healthy volunteers	84% take rate, inferior to Dryvax; GMT of NAb not inferior to Dryvax	Local reactogenicity common; no differences in SAEs between groups; 1 case of generalized VACV in Dryvax group
CCSV (DynPort)	91 VACV-naïve healthy volunteers	IM route least immunogenic; ID route more immunogenic if pock lesion develops	Reactogenicity symptoms lower with ID or IM route and no serious AEs	[48,67]
	150 VACV-naïve healthy volunteers 100 VACV-experienced healthy volunteers 100 VACV-naïve healthy volunteers (dilution subgroup)	99.7% developed take responses; immunogenic even at 1:50 dilution	No SAEs; no difference in local or systemic reactogenicity between CCSV & Dryvax; more systemic symptoms in naïve subjects
CJ-50300	24 VACV-naïve healthy volunteers	100% take rate and seroconversion, 100% response rate by ELISPOT	Not reported	[69,70]
	123 VACV-naïve healthy volunteers	99% take rate and seroconversion with one dose; 91% response rate by ELISPOT	Local and systemic reactogenicity similar between high dose and low dose groups; no cases of myopericarditis; one possible case of generalized VACV

Abbreviations: VACV – vaccinia virus; AEs – adverse events; SAEs – serious adverse events; ID – intradermal; SC – subcutaneous; IM – intramuscular; EKG – electrocardiogram; GMT – geometric mean titer

¹Subjects enrolled are enumerated in the tables, but not all subjects completed the respective studies or could be included in the final analyses.