Table 1. Smallpox vaccines and vaccine candidates (2008).
| Platform | Product | Parent strain | Rationale for its use |
|---|---|---|---|
| First-generation | |||
| Lymph-derived vaccinia virus | Dryvax® (Wyeth) | NYCBH | Historical experience in the USA through the era of routine use |
| Sanofi Pasteur smallpox vaccine (SPSV) | NYCBH | Produced in 1956–1957 and used in the USA program of that era; in frozen storage since | |
| Elstree-RIVM (master seed stock held at the National Institute of Public Health in The Netherlands [RIVM]) | Lister | Historical experience in the Intensified Smallpox Eradication Programme | |
| Second-generation | |||
| Replication-competent tissue-cultured vaccinia virus | ACAM2000™ (Acambis): cloned virus grown in Vero cells | NYCBH | Defined manufacturing process; reduced theoretical risk of adventitious agents compared with lymph-derived vaccine; less neurovirulent in animal models |
| Elstree-BN (Bavarian-Nordic) | Lister | Defined manufacturing process; reduced theoretical risk of adventitious agents compared with lymph-derived vaccine | |
| Third-generation | |||
| Replication-competent, highly attenuated vaccinia virus |
LC16m8 vaccine: derived from 53 serial passages in rabbit kidney cells; temperature sensitive, small-plaque phenotype due to mutation in the B5R gene |
Lister |
Experience in more than 100,000 Japanese children between 1973 and 1975; better safety profile than traditional live vaccinia, less neurovirulent in animals but unproven clinical efficacy |
| Replication-deficient, highly attenuated vaccinia virus | MVA: derived from more than 570 serial passages in chicken embryo fibroblasts: IMVAMUNE (Bavarian-Nordic); TBC-MVA (Therion) | Ankara | Theoretically improved safety profile, especially for those in whom live vaccinia is contraindicated. Used in 120,000 primary vaccinees in Germany in 1970s but unproven clinical efficacy |
| NYVAC (Sanofi-Pasteur): attenuated by the deletion of 18 open-reading frames from a plaque-cloned vaccinia isolate | Copenhagen | Theoretically improved safety profile, especially for those in whom live vaccinia is contraindicated | |
| |
dVV-L: derived from deletion of UDG gene needed for viral replication |
Lister |
Theoretically improved safety profile and can be manufactured in cell line that complements UDG deficiency, thus increased capacity for rapid production |
| Subunit vaccines | Recombinant proteins; plasmid DNA | Vaccinia viruses, different sources | Theoretically improved safety profile |
MVA: Modified vaccinia Ankara; NYCBH: New York City Board of Health; UDG: Uracil DNA glycosylase.