038 - Immunization Against Vaccinia by Non-Infective Mixtures of Virus and Immune Serum

So about smallpox again. Obviously in full-blown smallpox, the skin lesions (see here) can cause some unsightly scarring. But even with the vaccine, an infection of cowpox/vaccinia virus can cause a few lesions and scars where it is inoculated into the skin, and this may not be ideal. So people wanted to see if they could improve the process and prevent this scarring.

One idea going around was, instead of using active virus by itself, mix it with serum from something already immunized with it, which would contain anti-vaccinia antibodies. This could prevent the virus from causing too bad an infection, while still allowing it to induce a good immune response.

So that's what today's study attempted.¹ C.P. Rhoads immunized 10 rabbits plus another 4 and with a mixture of vaccinia virus and serum from other rabbits that had been infected with vaccinia previously, so it was full of antibodies. Some other rabbits were kept un-vaccinated as negative controls.

Another interesting thing was that the test rabbits were inoculated by putting the mixture in their nose, rather than scraping it into the skin as usual. This was an unusual approach, so they had other rabbits inoculated in the skin the normal way as positive controls.

None of the rabbits immunized with the mixture had a negative reaction against the vaccine. Another rabbit got a vaccine of pure virus, no antibodies mixed in, and it produced the typical lesion that the virus makes.

So then the rabbits were challenged with the virus, and as expected, the negative controls produced the typical lesion that lasted a few weeks, but those immunized with mixtures previously only showed a small red spot that went away in 2 days.

Overall, the rabbits that received the mixture seemed to have good protection without a problematic response to the vaccine. Rhoads mentioned that it was important to have the correct proportions in the mixture though: too much serum and the vaccine wouldn't work well, but too little and the virus would form lesions as it normally did. Also, storing the mixture in a refrigerator was no good, since the virus escaped from the antibodies' clutches and wreaked its typical havoc.

Overall it seems interesting, but perhaps not very useful, especially if long-term storage isn't possible. And according to later studies, it might've been a misinterpretation somehow:

"The present work shows that a typical delayed hypersensitivity reaction in the absence of circulating antibody can be produced against vaccinia virus... Similar observations had been made in 1931 by Rhoads... The interpretation of his experiments was not clear at the time."²

Citations:
1. Rhoads, C. P. Immunization Against Vaccinia by Non-Infective Mixtures of Virus and Immune Serum. J Exp Med 53, 185–193 (1931).
2. Turk, J. L., Allison, A. C. & Oxman, M. N. Delayed Hypersensitivity in Relation to Vaccination and Multiplication of Vaccinia Virus in the Guineapig. The Lancet 279, 405–407 (1962).