Table 2.

Third-generation smallpox vaccines.

Vaccine	Subjects Enrolled	Findings	AEs/SAEs	Reference
IMVAMUNE (MVA-BN)	68 VACV-naïve and 18 VACV-experienced healthy volunteers	Dose-dependent seroconversion rates and NAb titers in VACV-naïve subjects, anamnestic responses in VACV-experienced	Mild-moderate local reactogenicity common; rare systemic reactogenicity	[87,89,91]
	90 healthy, VACV-naïve volunteers	MVA attenuates take following Dryvax and primes for higher antibody titers after Dryvax challenge	Mild-moderate local reactogenicity common; no SAEs related to vaccination
	165 VACV-naive volunteers	All subjects seroconverted after second dose; higher NAb titers with higher dose	Mild-moderate local reactogenicity common; no SAEs, no vaccine-related AEs
ACAM3000 MVA (Acambis/Sanofi)	72 healthy, VACV-naïve volunteers	Dose-dependent antibody titers; ID route immunogenic at 1/10th dose of IM or SC; MVA attenuates take and reduces viral shedding following Dryvax challenge	Local reactogenicity more pronounced with ID or SC injection than IM; no SAEs	[74,90]
TBC-MVA (Therion)	76 VACV-naïve and 75 VACV-experienced healthy volunteers	MVA attenuates take and reduces viral shedding following Dryvax challenge; MVA primes for increased CD8+ T cell responses after Dryvax	Local reactogenicity common; 3 exanthems following Dryvax challenge in placebo recipients	[88]
LC16m8	1529 VACV-naïve and 1692 VACV-experienced military personnel	94.4% vs 86.6% take responses and 90.2% vs 60% seroconversion respectively	No SAEs; one case of allergic dermatitis, one case of erythema multiforme	[72]
CVI-78	594 children with eczema 1009 patients (mostly 1– 5 years old) with eczema 95 healthy children	100% seroconversion, 87% take rate when given via scarification	Less reactogenicity than traditionally seen with Dryvax; no cases of eczema vaccinatum	[77,78,80,81]

Abbreviations: VACV – vaccinia virus; AEs – adverse events; SAEs – serious adverse events; ID – intradermal; SC – subcutaneous; IM - intramuscular