The antibody cocktail can change the way the world is fighting with flu

The extraordinary therapy developed in Jackson Laboratory (JAX) can change the way the world fights flu, one of the most deadly infectious diseases. In a new study, scientists report that the anti-camp cocktail has protected mice, including people with a weakened immune system-from almost every influenza strain, including bird and pig variants, which pose pandemic threats.

Unlike the current influenza treatments approved by the FDA, which are focused on viral enzymes and can quickly become useless when the virus mutations, this therapy did not allow viral escape, even after a month of repeated exposure to animals. This difference may be crucial in future explosions, when survival often depends on how fast and effective doctors can implement treatment and the development of vaccines will last about six months.

For the first time we saw such broad and permanent protection against flu in the living system. Even when we gave therapy a few days after infection, most of the treated mice survived. “

Silke Paust, immunologist from JAX and senior test author

Insight undermines the long belief that in order for antibodies to be useful as viruses, they must “neutralize” antibodies that are associated directly with viruses and block them from infecting cells. Instead, the team designed “non -neutral” antibodies that do not prevent infection, but mean infected lung cells and recruit the body’s immune system to clean the infection. This new approach can transform the way scientists design the treatment of other viruses.

“Most antibodies make our bodies, do not neutralize, but medicine has largely ignored them,” the pause explained. “We show that they can save lives. Even with deadly strains, such as H5 and H7, bird flu, this therapy saved life long after the infection stopped.”

The team focused on a small, highly conservative region of virus virus matrix, called M2E. This part of the virus is necessary for his life cycle and remains almost unchanged in all infected cells in all flu strains, including in human variants, birds and pigs.

The therapy did not lead to viral resistance even after a repetitive exposure, and sequencing did not confirm the mutation in the m2 region of the virus after 24 days of treatment. When testing the team effectiveness Three antibodies individually success was due to their connection, because this approach reduces the virus’s chances of escaping three different antibodies.

“The virus did not mutate, even using individual antibodies,” said Paust. “But in the flu season with millions of people taking this therapy, I would be much more sure that we can prevent escape from therapy if we use a cocktail.”

Paust and her team found that the antibodies were effective in low doses, both before and after influenza infection. The cocktail significantly reduced the severity of the disease and Viral load in the lungs and better survival indicators in both healthy and reduced mouse resistance.

When testing H7N9, a type of bird flu, which can be fatal for both animals and people, the team stated that only one dose of treatment reduced the amount of virus in the lungs, even when it was obtained four days after infection. Reduced viral loads correlated with better survival indicators. All mice survived when they treated antibodies with a cocktail in the first three days after the infection, while 70% and 60% survived in the fourth and five days respectively.

“We can use very low doses, which is also promising, because potential therapies can be cheaper and less likely that they cause undesirable side effects in humans,” said Paust.

Although the results are preliminary, they are promising for the future, in which patients can have access to therapeutic spare, who will be quickly arranged to combat seasonal epidemic or pandemic. Currently, flu vaccines are updated seasonally, because the virus is constantly forcing, which makes resistance to previous strains irrelevant.

“We need something that is outside the shelf, when we do not necessarily have time to create a new vaccine, if we have an explosion or a pandemic in which mortality is high, so this type of therapy can be easily accessible to everyone in every situation,” said Paust.

The team is working on designing antibodies for clinical trials. The idea is to create a “humanized” antibody with the same specificity to direct M2 protein, but without launching an immune response against therapy itself or reducing its effectiveness in humans. The team provides a future in which a cocktail could act as independent prevention for the elderly, reduced immunity and other high -risk groups, as well as serve as a therapy for seriously ill people with flu.

Other authors are Teha Kim from Jackson Laboratory; Lynn Bimler and Amber Y. Song of Baylor College of Medicine; Sydney L. Ronzulli, Scott K. Johnson, Cheryl A. Jones and S. Mark Tompkins from the Center for Influenza Disease & Emergence Research and Center for Vaccins and Immunology, University of Georgia.

The research was supported by Albert and Margaret Alkek Foundation, the National Institutes of Health (Grant R01Ai130065) and the National Institute of General Medical Sciences of National Institutes of Health (Grant AI053831).