[ Back to EurekAlert! ] Public release date: 14-Mar-2013
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine

2-pronged immune cell approach could lead to a universal shot against the flu

PHILADELPHIA - Seasonal epidemics of influenza result in nearly 36,000 deaths annually in the United States, according to the Centers for Disease Control. Current vaccines against the influenza virus elicit an antibody response specific for proteins on the outside of the virus, specifically the hemagglutinin (HA) protein.

Yearly vaccines are made by growing the flu virus in eggs. The viral envelope proteins, including HA, are cleaved off and used as the vaccine, but vary from year to year, depending on what flu strains are prevalent. However, high mutation rates in envelope HA proteins result in the emergence of new viral types each year, which elude neutralization by preexisting antibodies in the body (specifically the HA proteins' specific receptor binding sites that are the targets of neutralizing antibodies). On the other hand, other immune cell types are capable of mediating protection through recognition of other, more conserved parts of HAs or highly conserved internal proteins in the influenza virus.

E. John Wherry, PhD, associate professor of Microbiology and director of the Institute for Immunology at the Perelman School of Medicine, University of Pennsylvania, and colleagues, report in PLOS Pathogens that influenza virus-specific CD8+ T cells or virus-specific non-neutralizing antibodies are each relatively ineffective at conferring protective immunity alone. But, when combined, the virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity.

This synergistic improvement in protective immunity is dependent, at least in part, on other immune cells -- lung macrophages and phagocytes. An implication of this work is that immune responses targeting parts of the virus that are not highly variable can be combined for effective protection.

"The two-pronged approach is synergistic, so by enlisting two suboptimal vaccine approaches, we achieved a better effect than each alone in an experimental model," says Wherry. "Now, we are rethinking past approaches and looking for ways to combine T-cell vaccines and antibody vaccines to make a more effective combined vaccine."

"Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide protection in humans, and act as the basis for a potential 'universal' vaccine," says Wherry.

These results suggest a novel strategy that could potentially form a primary component of a universal influenza vaccine capable of providing long-lasting protection.

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Co-authors include Brian J. Laidlaw, Vilma Decman, Mohammed-Alkhatim A. Ali, Michael C. Abt, Amaya I. Wolf, Laurel A. Monticelli, Krystyna Mozdzanowska, Jill M. Angelosanto, David Artis, and Jan Erikson.

The research was supported by grants from the National Institute for Allergy and Infectious Diseases (HHSN272201100018C, AI077098).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital - the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.



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