If the H5N1 bird flu virus sparks a pandemic, older people may have better immunity than younger people because of past exposure to closely related viruses.
In previous clusters of H5N1 cases, older people were than younger individuals, so scientists hypothesised that the former group may have stronger immunity against the virus than those who are younger. This could be because older people have had more exposure to flu strains that are closely related to H5N1, called H1N1 and H2N2.
The 1918 flu pandemic was caused by the H1N1 subtype after it jumped from pigs to people. The descendants of this virus later infected almost all people worldwide until it was outcompeted by H2N2, which drove another pandemic in 1957. Versions of H2N2, which emerged after the H1N1 strain swapped genes with a bird flu virus, then spread globally until 1968. Another strain called H3N2, which isn’t closely related to H5N1, has dominated human flu cases since the 1970s.
Advertisement
To explore how past infections have shaped immunity against H5N1, at the University of Pennsylvania and his colleagues analysed blood samples collected from 121 people from Philadelphia, aged between 19 and 90 at the time of sampling, who were born between 1927 and 1998.
Around half of these people were born before 1968, making them 56 or older today. Almost all of this group would have caught H1N1 or H2N2 during their first flu encounter, and repeatedly later in life. “That first flu encounter seems to be especially crucial for later levels of immunity,” says Hensley. “Exactly why is an open question.”
In the blood samples, the researchers looked for antibodies against a protein called haemagglutinin that the virus uses to enter cells. In particular, they looked for those that could bind to a part of the protein called the stalk that is highly similar in H1N1, H2N2 and H5N1.
They found that people born before 1968 had around three times as many antibodies against the H5N1 stalk compared with those born later. By adding H5N1 and the antibodies to human kidney cells in a lab dish, the team found that the antibodies didn’t prevent infection, but could flag the virus to immune cells to destroy it.
These antibodies would reduce the risk of severe disease and death from an H5N1 infection, says at the University of Lisbon in Portugal. But antibodies are just one component of the immune response, with immune cells, including T-cells, also contributing to a person’s overall protection against flu. What’s more, the immune system wanes with age, so older people may still be at greater risk of severe symptoms despite having more protective antibodies, says Veldhoen.
The H5N1 influenza virus strain currently circulating worldwide has caused mass deaths in many , while cases in cattle have led to infections in .
At present, the strain is seemingly unable to pass from human to human, but as the virus evolves, it could gain the ability to do so. “It’s getting closer to human-to-human spread,” says Veldhoen.
In another experiment, Hensley and his colleagues analysed blood samples from 100 people born between 1918 and 2003 who took part in three H5N1 vaccine trials conducted around 2005. They found that initial levels of antibodies against the H5N1 virus were lower in children aged under 10 at the time of vaccination compared with adults, but, after vaccination, the increase in antibody levels was around eight times bigger in the younger than the older group.
This suggests that younger people might benefit more from vaccination, says at the University of Groningen in the Netherlands. However, larger studies are needed to establish how H5N1 immunity varies across today’s population, she says.
Such insights would help to guide vaccination strategies if H5N1 makes the leap to spreading between humans, says Huckriede. “I very much hope that’s not going to happen.”
medRxiv
