Another aspect of immunity in syphilis relates to the other treponematoses, yaws, bejel, and pinta. Anyone of these diseases protects in some degree against the others, in much the same way, although usually less effectively, that each protects against itself. This fact fits the pattern we saw much earlier, being offered by Hudson as evidence for his contention that the four treponematoses, including syphilis, are all variations of one disease. This "cross immunity" bears on the vaccine problem.

An effective vaccine must contain the particular antigen or antigens of the virus, cell, or toxin that give rise to the protective antibodies, treated if necessary so as to be harmless. The ideal vaccine would contain nothing else; but no vaccine has as yet achieved such ideal purity. Toxins are treated with formalin to make them nontoxic ("toroid"); viruses, and bacteria and other cells, are killed or inactivated, or otherwise modified so that at worst they produce a mild, localized, but immunizing infection as does cowpox virus, which is used as the live agent, producing the vaccination sore and scar most people still remember, normally a small price to pay for protection against smallpox. With syphilis it is unlikely that any comparable price would be tolerable. If a vaccine against syphilis could not be made harmless, the response to it, at the very least, would have to be mild and unquestionably self limiting, entirely distinct from syphilis and incapable of turning into syphilis.

There are two general approaches to such an objective. The first and more popular attempts to modify virulent spirochetes, taken either from rabbits or via continuing efforts to grow them in glass cultures. The second would approach the problem of reducing the virulence of the spirochetes by starting with the one from the mildest of the natural treponematoses pinta or possibly from one of the newly discovered African simian treponematoses. Let us look at these two in reverse order; the second, although potentially important, does not yet have much to be said for it.

The second approach is based in part on a finding reported in October, 1968, that the pinta spirochete, Treponema carateum, is sometimes infectious for chimpanzees. This spirochete, which Hackett thinks to be the most ancient and most highly adapted of the agents of treponematoses, had not previously been found infectious for rabbits or other animals, so that no basis was available for accumulating enough spirochetes for study, and especially for use as a vaccine. The 1968 report, by a cooperative team of workers from the VD laboratories in Atlanta and the Mexican Institute of Health and Tropical Diseases, is a brief preliminary statement dealing with only a few animals, and promising further details later. Whether this spirochete would be used directly to immunize human beings, or whether attempts would be made to modify it so as to result in something less than naturally occurring pinta, has not been mentioned, although the author of a separate discussion of the subject hints at the second of these alternatives. Pinta is not a serious disease, but its bleached lesions are regarded as disfiguring, especially by dark skinned peoples, and might not be accepted as a satisfactory price for preventing syphilis by anybody but an albino. But there are at least two other difficulties in the path of the pinta vaccine for syphilis. One, shown in another brief report in 1970 by the same group but giving little new information, reveals that of three chimpanzees inoculated one was completely negative, another developed a darkfield positive lesion but no positive blood tests, while only one had both of these things but still failed to show any TPI antibodies presumably the important ones 183 days after inoculation. The second difficulty is that natural pinta is a disease of such slow development, and presumably manifests immunity, if at all, so much more slowly than does syphilis, that the prospect of using it to immunize against syphilis seems extremely dim. But this is an assessment and not a prediction; there were many who doubted that a polio vaccine could be developed. (see ANOTHER ASPECT OF IMMUNITY IN SYPHILIS PART II)