Antibody from experimental vaccine tricks bird flu

Those dreaded flu shots! You might wonder why we need them every year. Our blood contains red and white cells. The red blood cells shuttle oxygen across the body and the white cells provide immunity. The white blood cells include T cells and B cells. The B cells mature in the bone marrow, hence the name: B cells.

The B cells are like the “Special Agents” in the body’s adaptive immunity. Each B cell is tasked to recognize a single enemy, say, a strain of virus. The mature B cells produce “antibodies”, which are proteins tailored to fit very tightly around a part of the virus called “antigen”. When an antibody encounters its targeted antigen, it binds with it very tightly, rendering the antigen harmless. This is the mechanism which protects us after immunization, against a weakened virus.

Among the B cells, the Memory B cells are like the wise old women of the tribe. They remember the old antigens – the viral strains, long after the infection is cured and has since forgotten by the younger B cells. The yearly vaccination awakens and boosts those already existing memory B-cells to recognize closely related seasonal viral strains. But when a new virus, like the bird flu virus – H5N1 strikes, we have no pre-existing immunity.

The viruses wear a coat of proteins called hemagglutinin (H) and neuraminidase (N). They use these HN proteins to latch onto the receptors of their choice on our cells. After latching, the viruses gain entry to our cells by hitchhiking transporter proteins of our cell. These HN spikes make flu viruses different from each other: much like a porcupine from a hedgehog! Flu viruses can have any of the 18 different H subtypes and 11 different N subtypes. The H1N1 is the seasonal flu virus, but the H5N1 is a never before seen strain. The H5N1 virus does not anchor well to humans yet because it needs a special kind of sugar link – alpha (2,3) on its target. The alpha (2,3) link is common in ducks, but is rare in humans. However, fast evolving viruses can quickly acquire a new deadly skill: to anchor well with the type of sugar link the humans have – alpha (2,6).

An answer

Thankfully, Vanderbilt University researchers Ben Spiller, James Crowe, and colleagues have previously shown an experimental vaccine that can produce antibodies capable of killing a potentially very dangerous H5N1 strain created in laboratory. From the blood of a healthy donor, who was injected with the experimental vaccine during a clinical trial, they isolated a highly potent antibody.

Now, these same scientists have also discovered how this antibody neutralizes the bird flu virus. Writing in the Proceeding of the National Academy of Sciences, they describe that this antibody – H5.3 poses like the type of the sugar link – alpha (2,3) the virus needs to latch onto human cells. The antibody then alters its structure after binding with the hemagglutinin spike of the bird flu virus, in an unprecedented manner.

The Vanderbilt scientists highlighted that the antibody is highly flexible and has a changeable structure like other still maturing antibodies. They emphasized that repeated “challenges” through immunization or infections are the best way to maintain a robust immunity against continuously evolving viruses. They also suggested that a “universal flu vaccine” thus may require multiple exposures against diverse antigens.