Could Llamas Be the Missing Link for Flu Vaccines?

Influenza kills between 250,000 and 400,000 people worldwide every year, according to estimates by the World Health Organisation. In the UK, around 600 people die annually of flu complications. However, some years are much worse than others; in the 2008-2009 flu season, an estimated 13,000+ deaths were caused by the flu in the UK alone.

The flu is caused by influenza viruses, members of the Orthomyxovirus family. These viruses have an RNA genome that works similarly to our DNA – when the virus infects a cell, the cell reads the virus RNA, and makes the virus’ proteins, in a process called translation. The viral genome mutates frequently, resulting in many different strains of influenza virus.

Currently, we can’t produce a vaccine effective against all strains of influenza virus, instead making vaccines which provide immunity against individual strains. Around 8 months before peak flu season, experts design that year’s vaccine against influenza. They predict the three or four strains of influenza which they believe will be most prevalent, and build a vaccine protecting against all of these.

However, influenza is unpredictable; when flu season comes, there may be an abundance of an influenza virus strain which the designed vaccine doesn’t protect against. Because of this, the exact level of protection that flu vaccines can offer varies from year to year.

A recent study, published on November 2nd (Laursen et al.), has suggested that llama antibodies might be key in creating a vaccine which protects against all influenza viruses.

Antibodies work by recognising molecules in the body that don’t belong to the host, such as proteins on the surface of a virus. These molecules are called antigens. Antibodies bind to antigens, neutralising them and alerting the host’s immune system to the presence of a foreign body.

Vaccines contain antigens for a particular pathogen (such as influenza). When injected into the body, host antibodies bind to these antigens, triggering an immune response. After the immune system has encountered an antigen, it creates memory cells specific to the molecule. If the host encounters that same antigen again, the immune system is able to respond much more quickly because of these memory cells. This is how vaccines work; they expose the host to a particular antigen from a pathogen, so if the pathogen infects the host at a later date, the immune system can respond more efficiently.

Llama antibodies are much smaller than human antibodies. When human antibodies encounter influenza, they bind to the HA proteins which stick out from its surface. These proteins differ greatly between strains of influenza virus, and therefore a vaccine which protects against one strain might not protect against another. However, the smaller llama antibodies can navigate past influenza’s HA protein spikes, binding to other parts of the virus particle which don’t change between strains.

These llama antibodies, after encountering one strain of influenza virus, seem to have an increased immune response against all strains. This broad range of immunity is what influenza vaccines are currently lacking.

The researchers infected llamas with influenza virus, then selected four of the llamas’ antibodies which appeared to give immunity against all influenza species. They combined elements of all four antibodies to synthesise their own, similar antibody. The researchers infected mice with influenza doses which should have been fatal, then injected the mice with the newly designed antibody. The mice were infected with 60 different influenza strains; only one strain wasn’t neutralised by the antibody, and this strain doesn’t infect humans. The synthetic antibody proved to be very effective in mouse models.

Although promising, this research is still in the very early stages. The team involved have said further research is needed before human trials could be considered. Nonetheless, there is high demand for an influenza vaccine which can work against a broad range of virus strains, and this study provides hope that that may be the case in the not-too-distant future.

image source: www.veteranstoday. com/