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In the first half of the 20th century, people felt helpless and afraid in the face of poliomyelitis, an infectious disease that attacked the nervous system and often led to permanent paralysis. No vaccine became available for polio until 1955, when American physician Jonas E. Salk’s vaccine was approved for marketing. Salk explained how his vaccine worked in the following 1955 article for Scientific American. After widespread vaccination began, cases of poliomyelitis in the United States plummeted. In 1991 polio was declared eradicated in the Western Hemisphere.
By Jonas E. Salk
We shall soon learn the results of last year's extensive field test of the vaccine against poliomyelitis. Whatever the analysis of that test shows, the type of vaccine that is being tested will continue to be an issue among virologists, because an immunological principle is under test as well as a vaccine. The vaccine in question is made of a 'killed' virus, that is, a virus rendered noninfectious by treatment with formaldehyde. Many virologists believe such a vaccine can never be as effective as one containing live virus, and that the best hope of conquering poliomyelitis is to develop a safe live-virus vaccine. The question has been discussed at a number of recent meetings. I share the view that a killed-virus vaccine not only avoids the hazards of live virus but, if properly prepared and used, may be just as effective in producing immunity. This article will present some findings that bear on the questions involved.
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Many authorities have long held the view that 'there is no immunity like convalescent immunity,' meaning the immunity a person acquires after recovery from infection. Poliomyelitis is considered a particularly good illustration of this principle, because infection with the virus seems to give lifelong immunity to those who recover. Pursuing this reasoning further, proponents of the live-microbe approach point to the success of the live-virus vaccines against smallpox and yellow fever, and observe that no human virus disease has yet been brought under control by a killed-virus vaccine.
In reply it is possible to point out that convalescent immunity is not always permanent or absolute. The smallpox vaccine, made of a modified virus, usually does not confer lifelong immunity, one indication of which is that travelers abroad must be revaccinated if they have not been vaccinated within three years. And there is no lasting immunity after infection by a virus of influenza or the common cold. In the case of poliomyelitis we have strong reasons to seek a solution which will avoid the risk of putting the live virus in human beings. On the basis of studies of both poliomyelitis and influenza, there is every reason to believe that a killed-virus vaccine can work, and that the failures of such vaccines hitherto have been due not to inherent limitations but to the way they were prepared or used.
The theory of the killed-virus vaccine rests on the well-established fact that an inactivated virus, though it has lost the power to infect or multiply, may still act as an antigen stimulating the body to produce antibodies against the specific virus. That the present vaccine can evoke these antibodies has been proved abundantly. The chief question is how long immunity will last. The vaccine under test has not been in use long enough to give an answer. But we have some clues.
A monkey that has been vaccinated with the killed-virus vaccine at a certain strength will resist a paralyzing dose of poliomyelitis virus injected into its blood. When the vaccine is diluted to one part in four, it still prevents paralysis in every case. Indeed, six out of 10 monkeys suffer no paralysis, as one experiment showed, even when the vaccine is diluted to one part in 256. A vaccine dilution that produces a barely detectable level of antibody in the bloodstream is sufficient to prevent the virus from invading the central nervous system from the blood. The vaccine will prevent paralysis in monkeys even if the virus is introduced into the nervous system, but in that case a somewhat higher level of antibody is required.
Now let us see what happens to the antibody level in human beings when they are vaccinated. As is now well known, there are three poliomyelitis viruses—three different types with more or less independent powers of infection. In a typical U. S. population a majority of the children are not exposed to the virus during their early years, but as they grow older most of them are attacked by the virus (usually to only a mild, unnoticed degree) and gradually acquire antibodies to one or more of the virus types. Suppose we inject the killed-virus vaccine into two groups, one consisting of persons who have no detectable antibody and the other of persons who have some antibody from an infection at some time in the past. …the vaccination has a strong booster effect in the persons who already have some antibody, increasing the amount of antibody against the three virus types to a high level.
We can get the same booster effect by vaccinating previously uninfected persons two or three times at suitably spaced intervals. How long should these intervals be? …doses given two and five weeks after the first dose add comparatively little to the antibody level. For the full booster effect, we deduce from studies still not completed, a secondary dose should be given between four and seven months after the primary set of inoculations.
How long will the immunizing effect last? That depends on the capacity of the antigen (the killed poliomyelitis virus) not only to incite antibody formation but also to leave a lasting impression upon the 'conditioned' body cells that form the antibody. Some strains of the virus seem to call forth antibody more easily than others. In fact, this accounts for the potency of very small doses of the vaccine. By experimenting with the various strains we have been able to develop vaccines more potent than those with which we started.
We have learned recently that one virus type may have antigenic components like those in another, so that one may call forth antibodies which are also active against the other. For instance, an infection with the type 2 virus seems to reduce the chances that a later infection by type 1 will produce paralysis. This is highly significant, because the type 1 virus appears to be more dangerous than type 2 or 3: among hundreds of paralyzed poliomyelitis patients examined, infection by type 1 was eight times as frequent as by type 2 or 3.
Now a number of tests show that antibody persists for an appreciable time after vaccination with the killed-virus vaccine. Even after a single dose of the relatively weak preparations used when this vaccine was first made, most of the persons vaccinated had detectable levels of antibody a year after the inoculation. But even more interesting is the fact that when an individual is given a booster injection of the killed vaccine some months after the first, the antibody jumps to a high level—often higher than that after natural infection. This jump occurs even when the second injection is given as long as two years after the first.
Evidently the first exposure to the antigen, whether it is the killed virus or live virus in a natural infection, heightens the reactivity of the body to the antigen. In this hyperreactive state the body responds with rapid formation of antibody to a second invasion, either by live or by killed virus. We do not yet know whether immunity depends on this hyperreactivity or on the actual level of antibody present in the blood. Whichever is the case, the killed vaccine seems to meet both requirements: it produces the hyperreactive state and it maintains antibody in the blood, especially when a booster dose is given some months after the initial vaccination.
Our recent studies suggest that hyperreactivity may be sufficient. Apparently infection with the type 2 virus makes some persons hyperreactive to the type 1 virus, and such individuals seem to be able to resist type 1 paralysis even though there is no measurable antibody against that specific virus in their blood at the time of exposure. This must mean that the new exposure to type 1 causes the sensitized individual to produce type 1 antibody rapidly enough to block the invading virus before it can reach the central nervous system, or perhaps even before it gets into the blood.
This concept of the dynamics of the immunizing process suggests a new outlook toward infectious diseases that behave like poliomyelitis. If the concept is correct, we should test immunity by testing for hyperreactivity. Tests for the degree of hyperreactivity, based on the response to a booster injection, are now being devised. The booster injection would thus serve a double function against poliomyelitis—a test for immunity and a stimulus for the production of more protective antibody.
Source: Reprinted with permission. Copyright © April 1955 by Scientific American, Inc. All rights reserved.
Appears in
Salk, Jonas Edward; Virus (life science); Poliomyelitis; Immunization
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