Antibody research paves way for new, better flu drugs

In the US alone, these epidemics are estimated to account for 3.1 million hospitalization days and a loss of $10.4 billion in direct medical costs.

SEPTEMBER 20, 2014 23:15

Four year-old Jonathan Nies reacts as he receives a flu vaccination at Children's Hospital Boston in Boston, Massachusetts. (photo credit: REUTERS) — Four year-old Jonathan Nies reacts as he receives a flu vaccination at Children's Hospital Boston in Boston, Massachusetts.

(photo credit: REUTERS)

Seasonal influenza is a major health problem around the world, as epidemics – mostly in the fall and winter – cause some three to five million cases of severe illness, leading to between 250,000 and 500,000 deaths worldwide. In the US alone, these epidemics are estimated to account for 3.1 million hospitalization days and a loss of $10.4 billion in direct medical costs.

Research toward developing new antibodies at the Hebrew University’s Faculty of Medicine could pave the way for more effective drugs to combat flu infection. “It is thus urgent to develop new drugs for fighting influenza infection, which requires an understanding of the virus’s life cycle and its interaction with the host’s immune system,” said Yotam Bar-On, a doctoral candidate in immunology and cancer research.

Bar-On conducted his research under Prof. Ofer Mandelboim of the Lautenberg Center for General and Tumor Immunology, at the Institute for Medical Research Israel-Canada in the medical faculty. The research earned Bar-On a Kaye Innovation Award, which was presented to him earlier this summer.

In the past, said Bar-On, it was shown that natural killer (NK) cells belonging to the body’s immune system can eliminate cells infected with flu virus. This is made possible by one of the major NK killing receptors, NKp46, which recognizes influenza virus expressed on the infected cells.

But a problem arises from the fact that the viruses have a unique mechanism to evade attack that is mediated by the neuraminidase (NA) protein.

NA counterattacks NKp46 recognition of infected cells and reduces its ability to eliminate them.

Bar-On showed for the first time that NA inhibitors – which are already commonly used to treat influenza infections – enhance the NKp46-mediated killing of infected cells. Through further research into peptide components of the NA protein, Bar-On was able to develop antibodies that can to bind the NA, in effect “tying them up” and taking them out of action.

His work has been patented through Yissum, the HU’s technology transfer company, which is seeking commercial partners to continue research and development. Bar-On is currently working on generating cross-reactive, anti-influenza antibodies that will bind the NA proteins in most of the influenza virus strains known today. He has shown that when injected into mice infected with flu virus, these antibodies significantly improved their survival.

Bar-On’s work is expected to make possible future new and more efficient drugs that will both target NA and at the same time more efficiently boost the NKp46-mediated killing of influenza virus. “Altogether, the novel antibodies we have developed will allow our immune system to respond more efficiently to a wide variety of influenza infections,” he concluded.

DRINKABLE SUNSCREEN TO PROTECT SKIN?

From lotions to sprays to sticks, consumers already have a myriad of options to choose from when selecting a sunscreen. Now, several additional sun protection tools have become available, including sunscreen pills, drinkable sunscreen and ultraviolet (UV) light monitoring bracelets.

To help consumers make smart decisions when protecting their skin from the sun, dermatology Prof. Henry Lim at Henry Ford Hospital in Detroit noted recently that 20 percent of Americans will get skin cancer in their lifetime even though it is preventable. “While taking a pill sounds like a more convenient way to protect the skin, seeking shade, wearing protective clothing and applying a broad-spectrum, water-resistant sunscreen with an SPF of at least 30 are still the most reliable methods of sun protection.”

Of the ingredients found in experimental sunscreen pills, Lim said the strongest research is linked to Polypodium leucotomos, an extract of a Central American fern plant. Studies have shown the fern extract increases the amount of time it takes for skin to burn when exposed to UV light. “We’re not completely sure how sunscreen pills work, but the main understanding is that Polypodium leucotomos acts as an antioxidant, so it protects the skin from oxidative damage caused by sun exposure,” said Lim.

Lim also said European studies have shown Polypodium leucotomos can reduce sun sensitivity in people with polymorphous light eruption, a condition that causes an itchy rash when skin is exposed to the sun.

While pills with Polypodium leucotomos cannot be given a sun protection factor (SPF) rating because the product is not applied to the skin, Lim said studies comparing the level of protection with that of a traditional sunscreen show the fern extract pill provides the equivalent to an SPF of only 3 to 5. The level of protection is significantly less than the American Academy of Dermatology’s recommendation to use a sunscreen with an SPF of 30 or higher.

Other antioxidants, such as green tea extracts and vitamins C and E, also have been shown to offer protective effect from sun damage. Studies have been done on green tea extracts applied to the skin, while vitamin C and E have been studied when taken orally.

“If someone wants to take a sunscreen pill, they should continue protecting their skin by seeking shade, wearing protective clothing, and applying sunscreen,” said Lim. “While there have been promising results, more research needs to be done to know the optimal way of using these pills and their long-term safety.”

New UV-monitoring bracelets have been developed to help people track their sun exposure and monitor the intensity of UV rays. “Personal UV-monitoring is an interesting development. It could help increase awareness of the need for sun protection by the general public,” said Lim. However, he questioned the reliability of the product, noting it wasn’t sure that they measure UV levels constantly. He recommend that people in the sun reapply sunscreen every two hours and after swimming or sweating.