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H1N1 Survivors May Hold Answer to Universal Vaccine

The search for a universal flu vaccine has received a boost from the surprising source: the 2009 H1N1 pandemic flu strain.

Several patients have contracted this year’s H1N1 strain developed antibodies that are protective against a variety of flu strains, scientists from Emory University Med school and the University of Chicago have discovered. The results were published online Monday within the Journal of Experimental Medicine.

“Our data implies that infection using the 2009 pandemic influenza strain could induce broadly protective antibodies which are only rarely seen after seasonal flu infections or flu shots,” says first author Jens Wrammert, PhD, assistant professor of microbiology and immunology at Emory University School of Medicine and the Emory Vaccine Center.

“These findings show that these kinds of antibodies could be induced in humans, when the defense mechanisms has got the right stimulation, and claim that a pan-influenza vaccine might be feasible.”

The antibodies isolated from the group of patients who were infected with this year’s H1N1 strain could guide researchers in efforts to create a vaccine that provides people long-lasting protection against a large spectrum of flu viruses, say the researchers. Next, the research team is planning to examine the immune responses of people who were vaccinated against the 2009 H1N1 strain but didn’t become ill.

The research develops from a collaboration between the laboratories of Rafi Ahmed, PhD, at Emory and Patrick Wilson, PhD at the University of Chicago. Ahmed is director of the Emory Vaccine Center along with a Georgia Research Alliance Eminent Scholar. Wilson is assistant professor of medicine in the University of Chicago’s Knapp Center for Lupus and Immunology Research.

Scientists from Columbia, Harvard and also the National Institutes of Health (NIH) also led to the research, which was funded by the National Institute of Allergy and Infectious Diseases, area of the NIH, and by the American Recovery and Reinvestment Act of 2009.

The nine patients studied were recruited with the Hope Clinic, the clinical division of the Emory Vaccine Center. They’d a range of disease severities, from mild illness that waned after a couple of days to some severe case that required a two-month hospital stay including ventilator support. The majority of the participants were in their 20s or 30s. Liquid blood samples were usually taken about Ten days following the onset of symptoms.

The team of researchers identified white blood cells in the patients that made antibodies against influenza, and then isolated the antibody genes from individual cells. They used the genes to produce antibodies in cell culture a total of 86 varieties and then tested which flu strains they reacted against.

Five antibodies isolated through the team could bind all the seasonal H1N1 flu strains from the last decade, the devastating “Spanish flu” strain from 1918 and also a pathogenic H5N1 avian flu strain.

Seasonal flu shots contain three inactivated viral strains, each grown in chicken eggs. During the last decade, it had been standard that one of the three is definitely an H1N1 strain. However, vaccination with anyone H1N1 strain doesn’t usually result in protection against all of them ““ that’s why this year’s strain could make so many people sick.

Some of the antibodies the team identified keep to the “stalk” region of part of the virus (a protein called hemagglutinin). Because this part of the virus doesn’t change around other regions, scientists have proposed to make it the basis of a vaccine that could provide broader protection.

“Previously, this type of broadly protective, stalk-reactive antibody was regarded as unusual,” Wrammert says. “In contrast, in the patients we studied, these stalk-reactive antibodies were surprisingly abundant.”

The team tested whether three of the antibodies they isolated could protect mice from the 2009 H1N1 strain or two other common lab strains. Two antibodies could protect mice against a normally lethal dose associated with a of the three strains, even if the antibody was given 60 hours after infection. However, one antibody only shielded from the 2009 H1N1 strain.

The antibody that just reacted towards the 2009 H1N1 strain came from the patient most abundant in severe illness. The antibody genes from that patient claim that the patient had a complete insufficient preexisting immunity to H1N1 viruses, the authors write. In instances where patients experienced a milder illness, it seems that immune cells that coded in reaction to previous seasonal flu shots or infections formed a basis of response to 2009 strain.

“The result is something similar to the Holy Grail for flu-vaccine research,” says study author Patrick Wilson, PhD, assistant professor of drugs in the University of Chicago. “It demonstrates how to make a single vaccine that may potentially provide permanent immunity to all influenza. The surprise was that this type of completely different influenza strain, instead of the most typical strains, could lead us to something so widely applicable.”

Additional authors include Dimitrios Koputsananos, Gui-Mei Li, Srilatha Edupuganti, Megan McCausland, Ionna Slountzou, Behzag Razavi. Carlos Del Rio, Rama Rao Amara, Youliang Wang, Mark Mulligan, Richard Compans, and Aneesh Mehta from Emory University; Michael Morrissey, Nai-Ying Zheng, Jane-Hwei Lee, Min Huang, Zahida Ali, Kaval Kaur, and Sara Andrews from the University of Chicago; Mady Hornig and Ian Lipkin of Columbia University; Jinhua Sui and Wayne Marasco of Harvard School of medicine; Suman Das, Christopher O’Donnell, Jon Yewdell and Kanta Subbarao from the NIH.

Drs. Ahmed and Wrammert and Emory University have entitlement to royalties based on the sale of products related to the research described in this paper. This research may affect their personal financial status. The relation to this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies.

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