013 - The Opsonic Index as a Guide to regulate the use of Vaccines in the Treatment of Disease

This paper seems to be near to the inception of immunology, obviously an important area of research into the mechanism and function of vaccines. The authors report on work done by a number of researchers (mostly women, interestingly) evaluating the opsonic index, mentioned here before.

To recap: the opsonic or phagocytic index is a measure of the activity of white blood cells in consuming bacteria they encounter.

Research previous to this paper had discovered that the increased activity of the white blood cells (aka leukocytes) of vaccinated animals was not something inherent to the cells themselves—isolated leukocytes from unvaccinated animals had the same activity. Rather, the increased activity came from some other component of the serum of the animal (the liquid, cell-free portion of the blood). A.E. Wright referred to this serum element as "opsonins," which bind to the pathogen and induce phagocytosis, that is, uptake by white blood cells.

According to Wright, who developed the opsonic index method, determining this index value is important for administering vaccine therapy, because too high a dose can actually reduce a person's immunity to a pathogen.

The way this opsonic index is determined is to take equal amounts of bacteria, blood cells, and serum and mix them together, incubate for 15 minutes, then examine them under a microscope and count how many bacteria each leukocyte has taken up into itself.

The authors here describe a number of factors that must be controlled to get an accurate opsonic index value; failure to control them can introduce significant artifical variation. Such factors include number of leukocytes counted from each sample (at least 50 is important, up to 150; speaking from experience, that sounds like a seriously unpleasant experience for the person doing the counting, staring into a microscope for so long; especially since it is also important for just one person to do all the counting, since different people count the numbers differently and induce more variation), and slight variations in mixture proportions can introduce variation too. Because of these difficulties, it often took so long to finish a counting that the vaccinator had to go ahead and treat the patient before actually getting the results.

There was some investigation into the nature of these opsonins, too. Those from unvaccinated serum were more vulnerable to disruption by heating than those from vaccinated, and the former seemed to bind more generally—they could be titrated or removed from the serum using common "complement absorber" compounds—whereas the elements from vaccinated serum were more heat-stable and only bound well to the pathogens that had been vaccinated against. The latter, they referred to as "antibodies." We know more about these elements in modern times, of course, as members of the innate vs. adaptive immune systems.

The authors also report a number of trials of vaccine therapy against a variety of pathogens, using opsonic index measurements to inform the therapy. In most of the cases it didn't seem to help very much, and the index readings were inconsistent, so it didn't seem as useful as Wright made it out to be.

Citation: Park, W. H. & Biggs, H. M. The Opsonic Index as a Guide to regulate the use of Vaccines in the Treatment of Disease. J Med Res 17, 77–88 (1907).