032 - Duration of Immunity Following Modern Smallpox Vaccine Inoculation

Safety and effectiveness are two important things with vaccines, but something else that is important to consider (that is also maybe part of effectiveness) is duration of immunity: how long someone is immune to a disease after being vaccinated against it. This varies considerably between different vaccines and diseases, depending on the strength and type of the immune response and on the pathogen itself, which may shift around its antigens so that the immune system no longer recognizes it (a good example of this is influenza).

So the study today is an attempt to get some handle on the duration of immunity to smallpox after inoculation with cowpox (aka vaccinia). Even in the days of Edward Jenner, some observed that people lost their immunity to smallpox sometime after being vaccinated. But the most specific they could say about that was that immunity lasted several years after one vaccination. It did seem that repeated exposure/inoculation led to more long-term immunity, such that if one were immunized three times about 5-6 years apart, immunity was life-long.

But in 1927, it was no longer legal to intentionally inoculate people with smallpox to test their immunity; at least not in Europe or the United States. No surprise. So researchers had to find other ways to determine immunity duration. Previous reports from Germany and Britain stated that immunity lasted 10 years on average, at which point it should be renewed, though a study in Algeria found a duration of only 5 years.

This article goes into some depth about proper vaccine technique and what reactions to expect when it's done right or not done right. Apparently many practitioners in the US were doing it wrong, in ways that had been banned in Europe. But when done right, the reaction observed in the patient's skin was an indication of how much immunity they had to cowpox before being inoculated, whether no immunity, partial, or full immunity. Though it wasn't clear exactly how much immunity to vaccinia paralleled immunity to smallpox; definitely a significant amount, of course.

So using these reactions, researchers tested the immunity of schoolchildren in California, inoculating them once in 1921 and then again in 1927, 6 years later. After the first round, the reactions indicated that about 55% had no immunity before inoculation (no surprise again), 12% had partial immunity, and 23% had full immunity somehow. The remainder didn't show any reaction from the vaccine, probably indicating poor vaccination technique.

Then after 6 years, they re-inoculated and observed reactions. If the vaccine worked well and immunity lasted at least 6 years, then perhaps 10% of subjects should show no or partial immunity from the re-test, while the rest should be fully immune. But actually, 1% had no immunity, 26% had partial, and 73% had full. So 15-25% of subjects had declined in their immunity after 6 years from the first inoculation.

This wasn't a great study by any means, but it was something, and should've been helpful in establishing a schedule for re-inoculation. Progress!

Citation: Gillihan, A. F. Duration of Immunity Following Modern Smallpox Vaccine Inoculation. Am J Public Health (N Y) 17, 906–911 (1927).