Smallpox: can we still learn from the journey to eradication?

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Smallpox, a devastating disease, was eradicated through vaccination.
• Edward Jenner pioneered smallpox vaccination, later popularized by Louis Pasteur.

Observation:

• Smallpox is an immunopathological disease manifesting as a systemic delayed type hypersensitivity (DTH) syndrome.
• Vaccinia virus, used as the vaccine, is closely related to a horsepox virus, not cowpox.
• Unlike variola (smallpox), vaccinia replicates locally, inducing a localized DTH response.

Findings:

• Variola circumvents innate immunity, leading to systemic spread.
• Vaccinia's localized replication and attenuation activate both innate and adaptive immunity.
• Replication-competent vaccinia is effective due to its ability to stimulate a robust immune response.

Implications:

• Vaccinia's efficacy as a vaccine provides a model for combating other infectious diseases.
• Replication-competent vaccinia virus holds promise as a vector for eradicating global pathogens.
• Understanding vaccinia's immunopathology is key to developing new vaccines and therapies.