Heart and lungs

First time flu infection may affect lifetime immunity

"A person's chances of falling ill from a new strain of flu are at least partly determined by the first strain they ever encountered, a study suggests," BBC News reports.

Researchers created a data analysis study, based on historic data, which aimed to look at the reasons why past flu epidemics of influenza A – commonly referred to as "bird flu" – have affected different age groups. It seems it comes down to the strains that were circulating when you were born.

Influenza A viruses carry two protein groups on their surface, H and N, which is how they are named, such as H1N1. There are two broad groups of H protein, and being exposed to one can imprint a lifelong immunity, or at least partial immunity, against another strain of the same group.

So for example, someone exposed to H3, a group two virus, when they were born was less likely to be affected by an outbreak of H7, another group two virus. The researchers call this "immune imprinting".

The findings may help in planning for flu outbreaks by estimating which age groups are most likely to be affected depending on what different strains of flu were prevalent when they were born

Where did the story come from?

The study was carried out by researchers from University of California, University of Arizona, and Fogarty International Center in Maryland, US. The individual researchers received various sources of financial support, including from the National Institute of General Medical Sciences of the National Institutes of Health.

The study was published in the peer reviewed journal Science Magazine on an open-access basis so it is free to access online.

The UK's media coverage of the study was accurate.

The lead researcher Dr Michael Worobey, was widely quoted, as he used the metaphor for describing the protein groups as "lollipops": "if you were first infected with a virus from the 'blue lollipop' group as a kid, that won't protect you against this novel, 'orange' strain".

What kind of research was this?

This was a data analysis using information from known human cases of the influenza A viruses H5N1 and H7N9 to investigate the theory that an individual's first encounter with a virus of this group will confer lifelong protection against others of the same group.

Influenza A viruses are all known to infect wild birds, hence are often termed "bird flu". They are characterised by the presence of two proteins on their surface called haemagglutinin (HA) and neuraminidase (NA) and this is how they are named, like H5N1.

There are various subtypes of flu according to HA group and these can be broadly categorised into two groups. For example, H1 and H5 fall within group 1, while H3 and H7 are in group two.

There have been several outbreaks of bird flu over the past 10 years, causing hundreds of severe cases of illness and some fatalities. However, among the human cases there were notable differences in age distribution. The possible reasons for this are not fully understood.

This study aimed to examine whether it could come down to the flu subtype that a person is first exposed to giving later protection against others of the same HA group. To do this the researchers looked at documented human cases of one group 1 virus, H5N1 and one group 2 virus, H7N9.

What did the research involve?

The researchers looked at whether an individual's initial exposure to an influenza A virus confers protection when later exposed to H5 or H7 viruses.

They looked at people born in each year from 1918 to 2015 for six countries – China, Egypt, Cambodia, Indonesia, Thailand, and Vietnam – and looked at the influenza A virus they were likely to have been exposed to in each year.

They also gathered data on the known cases of H5N1 and H7N9 and their age distributions. Most of these documented cases are the severe or fatal ones – the total number of cases is unknown.

What were the basic results?

The researchers made a number of observations.

Looking at the influenza A viruses that people have been exposed to over the years, strain H1N1, a group one virus, dominated between 1918 and 1957. H3N2, a group two virus, has then clearly dominated since 1968, with the notable exception of the peaks of H1N1 – aka "swine flu" – coinciding with the pandemics of 1977 and 2009.

Looking at an outbreak of H7N9 in China during 2012-15, there was a dominance of cases among people born in the first half of the 20th century.

Looking at H5N1 outbreaks in China, Egypt, Indonesia, Thailand, and Vietnam during 1997–2015, most cases occurred among people born from around 1968 onwards.

The researchers found that this was down to "HA imprinting". Across different HA subtypes, those in group one have more similarities than those in group two. Group one HA viruses show 83-98% similarity, compared to 76-82% similarity for influenza viruses in group two.

People born in the first half of the century had been exposed to a group one virus when they were born, so had no protection when later exposed to the group two virus, H7N9. People born in the second half of the century were exposed to a group two virus when they were born, so had no protection when later exposed to a group one virus, H5N1.

HA imprinting from child exposure was estimated to give 75% protection against severe infection and 80% protection against death from either H5N1 or H7N9.

They also estimated that people who become infected despite previous immunity, are probably at lower risk of infecting others because they have lower levels of viral shedding (the amount of viruses that are spread into the environment through actions such as sneezing).

They suggest that there has never been a true "virgin soil" flu pandemic because many people have protection from prior HA infection. That is, thankfully, there has never been a pandemic in which people had absolutely no level of immune protection against infection.

How did the researchers interpret the results?

The researchers conclude that their analysis of human cases of H5N1 and H7N9 shows strong evidence that childhood HA imprinting as a result of exposure gives lifelong protection against severe infection and death from these viruses.

They say "these findings allow us to develop new approaches for [influenza A virus] pandemic risk assessment, preparedness, and response but also raise possible challenges for future vaccination strategies."


This data analysis study shows how the HA group of influenza A – "bird flu" – circulating when a person is born give them lifelong protection against new subtypes within the same HA protein groups. The researchers call this immune imprinting.

This may help to explain the high severity and mortality rate seen among certain groups. For example, the massive flu pandemic of 1918 was an H1N1 strain.

This had a very high fatality rate among young adults, which the researchers consider may have been because when they were born (between 1880 and 1900), H3, a group two virus, was the dominant strain. Therefore they had no protection when encountering the group one virus H1. However, elderly adults of the same generation did have protection when H3 peaked in 1968.

These observations, however, aren't really too unexpected. It's already well known that the flu virus has many different strains; which is why people catch flu several times in their life, and why it's difficult to say the flu vaccine will definitely stop you catching flu (vaccines only cover the strain expected to be circulating that season). We also know that exposure to a specific virus gives us protection against the same if we encounter it again. So in that sense this isn't really "news" as such.

Nevertheless, as the researchers say, their findings could help in planning for future flu outbreaks, in knowing which age groups may be most at risk.

However as researchers acknowledge, analysis of documented cases of human flu typically looks at the more severe or fatal cases. Thousands of milder cases of flu may have missed medical attention.

The study also focused on examining cases in certain African and Asian countries. This may make it difficult to get the full picture of flu immunity.

For the general public there are limited immediate implications from this study. You can't change the year that you were born or the first strain of flu you were infected with.

You can reduce your risk of getting or spreading flu by following established hygiene advice. This includes regular handwashing, using tissues when you cough or sneeze then binning them after use.

The seasonal flu vaccine is available free on the NHS for pregnant women, anyone aged 65 and over, and adults with otherwise weakened immune systems or long-term health conditions.

A nasal spray form of the vaccine is now available; free of charge, for all children aged two to four, as well as older children with long-term health conditions.

Read more information about the seasonal flu jab for adults and the nasal spray for children.

NHS Attribution