Even in the days of smallpox some people objected to vaccinations.
Benjamin Franklin apparently “long regretted” his decision not to inoculate his oldest son, who died of smallpox at age 4 in 1736.
Yet skepticism over the vaccine persisted, even into the early 20th century when it was routinely required. By then, the virus had mutated to become less severe. Some argued the vaccine was no longer necessary and would create more risk than it resolved. Yet vaccination requirements continued, and smallpox remains the only disease ever eradicated from earth.

source