And researchers are investigating ways to develop other vaccines that are adjusted for the changes that happen in an older person’s immune system.
Last September, Dr. Ross received a $2 million subaward grant from the National Institute of Allergy and Infectious Diseases (NIAID), NIH to study immune and genetic responses to influenza during aging.
“This study will give us answers that will help us understand the difference between how people of different age groups respond to seasonal flu vaccine,” said Dr. Ross. His research team will focus the reactions in young children, adults, and the elderly to influenza infection so an improved, more protective flu vaccine can be developed for all age groups.
Other institutions receiving grants included the University of Pittsburgh, Mount Sinai School of Medicine-New York, and University Health Network-Toronto.
One approach to improving the immune response to vaccines in the elderly involved the use of a higher vaccine dose, an approach approved by the FDA in this population. “There are some reports that this caused a higher rate of seroconversion, about 50 percent,” Dr. Ross said. “But, as we have put this into practice, it doesn’t look like the high dose was much more effective for the elderly—still only between thirty and fifty percent. We want to get to eighty percent.”
“The other thing one can do,” he continued, “is to use adjuvants with the vaccine that cause a local inflammatory response, but these can cause a more severe reaction in an elderly person than a young person, as well as reduce compliance. Thus far the FDA has not approved the use of an adjuvant, although some that are currently approved in Europe are undergoing evaluation in the U.S.”
Dr. Ross is developing unique vaccines and testing them with these adjuvants, and attempting to develop a universal vaccine that can anticipate every potential strain that may occur as the flu changes.
Dr. Ross says in developing new vaccines his lab attempts to deal with viral antigenic diversity by using computer modeling to identify widening diversity among epitopes.
“We look at the phylogenetic information to examine consensus sequences that represent different eras of time, and we believe that we have captured the most significant epitopes that have appeared using bioinformatics analyses,” he explains. “Then we engineer those epitopes into a single flu hemmaglutinin molecule. Therefore, we can build a single molecule that contains all of the epitopes of flu over history. This vaccine can recognize epitopes over time and we hope this will continue into the future. Right now we would be happy with five to 10 years of immunity to avoid annual reformulation.
“What’s nice about the way we generate our vaccine is that you can put it into any platform a company is using, for example virus-like particles (VLPs), live attenuated, or any platform a company has.”
Dr. Ross has previously used this method to produce a vaccine against the H5N1 virus, commonly known as the bird flu. The vaccine, well tolerated in preclinical trials, successfully protects against known strains of bird flu. Dr. Ross and his VGTI Florida colleagues are applying similar strategies to fight other serious viruses such as West Nile Virus, dengue, and HIV Type 1 (HIV-1).
But even as researchers work to come up with a more protective flu vaccine for the elderly, a 2010 review published by the Cochrane Collaboration—an independent, nonprofit organization that promotes evidence-based medicine—concluded that “until such time as the role of vaccines for preventing influenza in the elderly is clarified, more comprehensive and effective strategies for the control of acute respiratory infections should be implemented.”