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Having the right weapon is the key to winning a battle, especially when the enemy is as powerful and adaptable as a virus. Eliciting the right antibody response—the right weapon—to fight back against deadly viruses like influenza, dengue and HIV is the key to effective vaccine research.

To that end, the National Institute of Health awarded a $2.8 million grant to Associate Professor Tim Whitehead’s lab to help better understand how the human immune system creates the right weapons: proper antibodies.

“Vaccines work in part because they elicit specific antibodies that recognize and neutralize a given pathogen,” Whitehead said. “However, these specific antibodies must be at sufficient concentrations to be effective, which is challenging for viruses like influenza or HIV. We have a long-term goal of making better vaccines; this specific grant will be used to help us understand why certain desirable anti-influenza antibodies are not selected by the human immune system.”

This award, titled “The influence of evolutionary landscapes on protective antibody development,” is a NIH Research Project Grant (R01), the oldest type of grant awarded by the organization. It will be paid out across five years.

Whitehead’s team includes ChBE graduate students Monica Kirby and Ali Borelli and a team of scientists at the University of Kansas under the leadership of co-principal investigator Brandon DeKosky.

“Our long-term objective is to map the lineage of antibodies in a way that enables us to predict how they might behave as a tool to manipulate the process of antibody selection,” Whitehead said. The research is motivated by the need to understand how effective antibodies develop to eventually create vaccines that will better counter deadly pathogens.

“This approach is innovative because it combines a unique hypothesis with state-of-the-art protein engineering tools needed to evaluate the hypothesis, and it is significant because the data generated here will illuminate why long-lasting, broadly neutralizing antibody responses to influenza hemagglutinin are so rare,” Whitehead said.

In other words: why doesn't the body always deploy the right amount of the most effective antibodies in the fight against the flu? But the research may have applications beyond just creating better common flu vaccines.

“The approach raised in this application may also expedite the design of effective vaccines, prophylactics and therapeutics against a range of human pathogens,” Whitehead said.