Combination Treatment Enhances Tetanus Vaccination

Dr. A. Catharine Ross, who holds the Dorothy Foehr Huck Chair inNutrition at Penn State, directed the study. She says, "There aren'tvery many examples of using nutrition to improve immune response. Theseresults show that a natural product of vitamin A can have an importantrole in regulating immunity and, when administered along with PIC,might be a potentially powerful nutritional-immunological assist invaccination."

The researchers reported their findings today (Monday, Sept.12) in the online early edition of the Proceedings of the NationalAcademy of Sciences. The paper is "The anti-tetanus immune response ofneonatal mice is augmented by retinoic acid combined withpolyriboinosinic: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 LifeSciences.

In previous studies, the Penn State researchers had shown thatretinoic acid boosts the adult mouse response to the tetanus vaccine.In the current investigation, they studied the response in week-oldmice. Mouse pups, like human infants, have a weaker response tovaccination than do adults due to the immaturity of their immunesystem.

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

In the most recent Penn State experiments, week-old mice weregiven oral doses of retinoic acid along with a tetanus shot. The pupsthat received the retinoic acid developed a four times better immuneresponse than mice that didn't receive the vitamin A product. Mice thatreceived both retinoic acid and, PIC, the synthetic immunity boosterpolyriboinosinic: polyribocytidylic acid, developed a seven timeshigher immune response.

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

Ross explains that the researchers measured three subtypes oftetanus antibodies in blood samples from the mouse pups aftervaccination. Both retinoic acid and PIC, when administered alone, eachincreased the antibodies about four-fold over all but the combinationretinoic acid/PIC treatment resulted in elevated levels that hadproportions of antibody types most like untreated pups.

Vitamin A is already given to children who are deficient inthis vitamin when they receive the measles ordiptheria-pertussis-tetanus vaccination and the intervention has beenshown to significantly elevate the vaccine-induced antibody responses.However, dosing non-deficient children with vitamin A cannot beexpected to have the same results as retinoic acid.

Ross explains that the human body makes retinoic acid fromingested vitamin A in very controlled amounts. Eating higher amounts ofvitamin A doesn't automatically result in higher levels of retinoicacid in the body.

The research was supportedby a grant from the National Institute of Health, the Penn State HuckInstitute for the Life Sciences and the Dorothy Foehr Huck Chair inNutrition.