Form and Function

Well I just realized that my last two entries are about TV. How scholarly of me. So here's a meatier one on the use of aluminum in vaccines.

Aluminum salts (aluminum hydroxide and aluminum phosphate, collectively called alum) are used in many vaccines as adjuvants - components that increase the vaccine's effectiveness when combined with other vaccine ingredients but do not independently create a targeted immune response to any particular disease. The use of adjuvants creates a stronger and longer-lasting vaccine-induced immune response for a given amount of antigen, thereby requiring less antigen per dose and decreasing production costs.

The modes by which aluminum enhances the immune response occur at the level of macrophage and T-cell function and include (not necessarily an exhaustive list, just what I could find online without feeling like I was researching a dissertation):
1. Increased uptake of antigen by the antigen-presenting cell¹.
2. Increase in antigen-induced T-cell proliferation¹.
3. Increased ability of macrophages to induce a antigen-specific memory response².

Questions arise over safety of aluminum use in vaccinations as excess levels of aluminum in the tissues can result if the kidneys are unable to secrete any excess, potentially resulting in impaired bone formation and impaired neurologic function. The FDA limits intravenous aluminum to no more than 4 to 5 micrograms per kilogram of body weight per day³ based on a 1997 study⁴ of premature infants indicating that these low levels are safe. Full-term infants and older children with good kidney function, receiving the aluminum intramuscularly, are likely able to tolerate greater amounts, but no studies meeting these criteria seem to exist⁵. Safe levels in vaccines are therefore not established, but current levels are very high in relation to the 4 to 5 micrograms per kilogram of body weight recommendation for IV medications.

For the sake of an example, amounts for the vaccines on the AAP schedule for the 2 month visit are given here⁵ (by brand, aluminum amount in micrograms):


HIB
- PedVaxHIB 225
- all other 0

Pc
- Prevnar 125

DTaP
- Tripedia 170
- Daptacel 330
- Infanrix 625

Rotovirus
- all brands 0

Polio
- Ipol 0

So an average infant at 2 months old, weighing about 4.5 kilos, could receive no more than 22.5 micrograms of aluminum intravenously as per the FDA (based on the AAP study), but would receive between 295 and 975 micrograms at their well-baby visit assuming all AAP-recommended vaccines are given.

Resources

1. Mannhalter, J. W., H. O. Neychev, G. J. Zlabinger, R. Ahmad, and M. M. Eibl. 1985. Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation. Clin. Exp. Immunol. 61:143-151.

2. Romaniol, A.C., et al. Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. Vaccine. 2004 Aug 13;22(23-24):3127-35.

3. http://www.fda.gov/ohrms/dockets/98fr/03-6227.html

4. Aluminum toxicity in infants and children, Committee on Nutrition, American Academy of Pediatrics, Pediatrics 1996; 97:413-416.

5. Sears, Robert W. The Vaccine Book. New York: Little, Brown and Company, 2007.

HBO has a new series out called True Blood about vampires able to make themselves public after a synthetic blood is developed by the Japanese that the vampires can consume in lieu of human blood. The plot revolves around Sookie, a human telepath, and her developing relationship with a vampire named Bill. When Sookie demands Bill tell her how he can be literally dead but seemingly alive, he tells her it's magic. When she scoffs he goes on to say:

"You think it's not magic that keeps you alive? Just 'cause you understand the mechanics of how something works doesn't make it any less of a miracle. Which is just another word for magic."

That's kind of how I've felt about taking A&P. No matter how much we know there will always be more that we have yet to lean. And the more we know the more we can wonder at the staggering complexity of what is.

There's a new show on TV called "The Drs." and the image above is from their set. I only watched a few minutes before being annoyed enough by several things to turn it off, but one of the most annoying is their set. There are some major problems with that attempt at an EKG reading along the front of the desk. That's one jacked-up P-wave and I bet it's hard to live without ventricular repolarization, eh?