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. 2016 Apr 28;15(9):1197–1211. doi: 10.1080/14760584.2016.1175305

Table 2.

Modern smallpox vaccines [71,101111].

Vaccine Original VACV strain Production method Usage Efficacy and reactogenicity Dose/route
Second-generation vaccines
ACAM2000 NYCBH Vero cells Part of US national stockpile, approved by FDA in 2008 Immunogenicity equivalent to Dryvax. Safety profile similar to Dryvax. 0.0025 mL of live VACV containing 2.5–12.5 × 105 pfu, 1 dose, percutaneous
CCSV (DynPort)* NYCBH MRC-5 cells Clinical trials Immunogenicity equivalent to Dryvax. Safety profile not well established. 1 Dose, delivered dose similar to Dryvax, percutaneous
Elstree-BN* Lister Chicken embryo fibroblast cells Clinical trials Similar efficacy and safety as Elstree/Lister. 1 Dose, percutaneous,
1 × 108 pfu/mL
CJ-50300 NYCBH MRC-5 cells Clinical trials Similar efficacy as Dryvax. 1 Dose, percutaneous, 1 × 108 pfu/mL
Third-generation vaccines
Live, attenuated vaccinia virus strains
MVA
(IMVAMUNE, TBC-MVA, ACAM3000)
Ankara, serially passaged in chicken embryo fibroblast cells Cell culture Used in 120,000 people at end of eradication.
Extensive clinical and animal trials.
Excellent safety profile. Immunogenicity may be lower than replication-competent vaccines. 2 Doses, subcutaneous, 5 × 107 TCID50
LC16m8 Lister, serially passaged in rabbit kidney cells Cell culture Used in Japan at the end of eradication. Stockpiled in Japan. Excellent safety profile. Similar reactogenicity to Dryvax. 1 Dose, percutaneous, ~4 uL of 1 × 108 pfu/mL
NYVAC Copenhagen, with genomic deletions Cell culture Early clinical trials 18 ORFs deleted, coding genes related to pathogenicity, virulence, and host range. Immunogenicity may be lower than live vaccines Likely 2 doses, intramuscular
dVV-L Lister, with deleted UDG enzyme Cell culture Animal trials Early animal studies show good immunogenicity and safety profiles in mice. Likely 2 doses, intramuscular, 1 × 106 pfu in mouse
Subunit vaccines
Protein-based, various Various   Nonhuman trials Theoretically better safety profile. Sufficient immunogenicity in animals when adjuvanted and boosted. 2–3 Doses, intramuscular, likely adjuvanted, human dosage TBD
DNA-based, various Various   Nonhuman trials Theoretically better safety profile. Sufficient immunogenicity in animals when adjuvanted and boosted. 2–3 Doses, intramuscular, likely adjuvanted, human dosage TBD

*No longer in development.