ISU researchers find possible alternative adjuvant for alum to boost the effectiveness of vaccines

Jul 29 2008

On the rocky road of cancer research, Indiana State University scientists have made important discoveries.

In developing vaccines for cancer and infectious diseases, researchers often trick the immune system by mixing "adjuvants" with the vaccines (proteins, killed cancer cell or infectious agents). "Adjuvants" are substances that jump start the immune system by making vaccines more effective.

ISU researchers have found a possible alternative adjuvant for alum to boost the effectiveness of a vaccine. Professor of life sciences, Swapan Ghosh's research team that includes undergraduate and graduate students has developed the adjuvant: phytol and derivatives, which are part of a chlorophyll molecule and vitamin E. Chlorophyll is the pigment in plants that participate in photosynthesis.

Alum is the most widely used adjuvant for humans. However, there is a need for better or alternative adjuvants, and researchers world wide are greatly interested in developing alternative adjuvants, partly because alum has come under attack as to a possible cause of neurological disorders.

"We found that this chlorophyll-derived adjuvant is actually unconventionally useful not only in enhancing cancer vaccines, but also in suppressing adverse autoimmune disorders," Ghosh said. "For example, against lupus, it actually prevents the development or slows down the development of lupus."

As to whether phytol derived adjuvants could be used with or in place of alum, Ghosh said that remains to be tested.

"What we have in mind, actually, is that we can use it by itself because this group of adjuvants also helps prevent Staphylococcus infections and E. coli infections," he said.

At this point, phytol-based adjuvants appear to have little or no toxicity. While on the hunt for effective cancer vaccines, Ghosh and his students' primary goal has been to find a nontoxic booster substance for use in vaccines for lymphoma. The adjuvant research has been published in the Journal of Immune Based Therapies and Vaccines.

"Cancer is not one disease," he said. "The only thing we can say is what we are offering is another weapon to develop treatment for diseases like cancer and infections. Right now, I'm using the blood cell cancers, which are lymphomas and leukemia, but I actually had previously worked on breast cancer and I possibly will handle some other cancers."

In addition to the antigen and adjuvant working together to attract white blood cells, Ghosh and his students seek an adjuvant that is not toxic as well as work is in boosting immunity.

"Vaccine-presenting cells of innate immunity must get attracted first when a vaccine is injected to alarm the immune system," Ghosh said. The immune system then builds up to attack the virus, bacteria or diseases like caner

Ghosh has also collaboration with Richard Kjonaas a professor with ISU's chemistry department and his students, who helped chemically modify phytol, as deemed necessary from Ghosh's research plan for vaccine design.

"We are hoping by developing this new phytol-type adjuvant to find a certain combination in vaccine formulations. This will allow our immune system to fight any abnormal growth like cancer in a specific way," said Youssef Aachoui, of Casablanca, Morocco, who is working on his doctorate in immunology and studying the adjuvant formulation. "What we're doing in our lab is we're trying to study the efficacy of this group of adjuvants in vitro, then in vivo."

Hongtao Li, who was a gynecological doctor in China and now as an ISU doctoral student studying the molecular basis of vaccines, is trying to find a way to evaluate cancer vaccines against lymphoma through the in vitro system.

"This is expected to cut down the use of animals and cut down the cost," she said "We would also know the mechanism about how vaccines are doing their job."

So far, researchers have been able to extend the life of mice with a vaccine.

"We have actually developed a vaccine which can prolong the life of mice three times," Ghosh said. "Our end point - can we get an animal totally tumor free? That's our objective. At this point we have been able only to increase their lifespan from 40 days, to 180 days in at least 25 percent of mice."

In the process of testing and seeking, an Indiana State researcher in Ghosh's Lab also made a discovery.

Nisreen Al-Shaibi a post-doctoral student from Qatar studying antigen-presenting cell biomarkers, helped identify a new protein, DP58 as a marker of the dendritic cell progenitor. Adjuvants are expected first to activate these types of cells and in vitro testing is underway. However the function of DP58 is unknown.

"We need to know the function of this protein in different places," Al-Shaibi said. "We're trying to discover this function."

Its function for now lies in the future, along with a possible cancer vaccine. Ghosh said for now he doesn't see everyone being vaccinated for cancer as people are for mumps, measles and rubella.

"Normal populations will not be vaccinated against cancer because you cannot predict that," he said. "It is only for those who have already had cancer and have gone through primary treatment. But some cancers which are hiding cannot be seen by a surgeon, a microscope or anything else. How do we tackle them? They are hiding, just biding time. Human cancer usually takes about 20 years before they can show up, so if before that, we can handle them, most likely the cure rate will be much higher."