Combination treatment enhances tetanus vaccination

In studies with mice, Penn State researchers have shown that a combination of retinoic acid — a product the body makes naturally from vitamin A — and PIC, a synthetic immunity booster, significantly elevates the immune system response to a tetanus shot.

Dr. A. Catharine Ross, who holds the Dorothy Foehr Huck Chair in Nutrition at Penn State, directed the study. She says, “There aren’t very many examples of using nutrition to improve immune response. These results show that a natural product of vitamin A can have an important role in regulating immunity and, when administered along with PIC, might be a potentially powerful nutritional-immunological assist in vaccination.”

The researchers reported their findings today (Monday, Sept. 12) in the online early edition of the Proceedings of the National Academy of Sciences. The paper is “The anti-tetanus immune response of neonatal mice is augmented by retinoic acid combined with polyriboinosinic:polyribocytidylic acid.” The first author is Yifan Ma, doctoral candidate in the Graduate Program in Integrative Biosciences, the Department of Nutritional Sciences and the Huck Institute for Life Sciences.

In previous studies, the Penn State researchers had shown that retinoic acid boosts the adult mouse response to the tetanus vaccine. In the current investigation, they studied the response in week-old mice. Mouse pups, like human infants, have a weaker response to vaccination than do adults due to the immaturity of their immune system.

Ross notes, “Strategies to enhance vaccination efficiency in early life are highly sought.”

In the most recent Penn State experiments, week-old mice were given oral doses of retinoic acid along with a tetanus shot. The pups that received the retinoic acid developed a four times better immune response than mice that didn’t receive the vitamin A product. Mice that received both retinoic acid and, PIC, the synthetic immunity booster polyriboinosinic: polyribocytidylic acid, developed a seven times higher immune response.

In addition, the researchers found that the combined retinoic acid/PIC treatment produced a more balanced enhancement than either retinoic acid or PIC alone.

Ross explains that the researchers measured three subtypes of tetanus antibodies in blood samples from the mouse pups after vaccination. Both retinoic acid and PIC, when administered alone, each increased the antibodies about four-fold over all but the combination retinoic acid/PIC treatment resulted in elevated levels that had proportions of antibody types most like untreated pups.

Vitamin A is already given to children who are deficient in this vitamin when they receive the measles or diptheria-pertussis-tetanus vaccination and the intervention has been shown to significantly elevate the vaccine-induced antibody responses. However, dosing non-deficient children with vitamin A cannot be expected to have the same results as retinoic acid.

Ross explains that the human body makes retinoic acid from ingested vitamin A in very controlled amounts. Eating higher amounts of vitamin A doesn’t automatically result in higher levels of retinoic acid in the body.