We continue to learn a great deal about influenza infection as researchers harvest information from the recent swine flu pandemic. The pork producers don’t like to call it “swine flu” but it may well be that its long sojourn in that animal since 1918 (did we give Spanish flu to pigs or did pigs give it us?) may hold an important clue to why older people suffered less than younger ones. It seemed fairly likely that the difference was related to immunity, but since H1N1 came back in 1977 after being absent since 1957, it wasn’t clear why younger people born after 1977 would be as immune as older ones born before 1957. Now two papers published in Science and Science Translational Medicine shed some light on this.
I’ve read both papers and the full story would take a lengthy post. Ordinarily that’s just what I’d do, but I’m still writing the grant so I’ll have to give an abbreviated version. There are news stories in both Science and Nature that will fill in some of the details from a different point of view. Furthermore, we’ve covered a lot of the basic science of receptors and such here, here, here, here, here, here, here, here. So I’ll assume some background and that this brief description will be comprehensible. If not, try the links above.
The flu virus is studded with two proteins, hemagglutinin (HA) and neuraminidase (NA), whose various subtypes give the different flu viruses their macro naming system, e.g., H1N1 being the first kind of 16 different hemagglutinin proteins and the first kind of 9 different neuriminidase proteins. The HA is involved in getting the virus into the host cell, so it is highly exposed, and it is this exposed part that the immune system “sees” and mounts an attack against. The business end of HA is a globular structure at the end of a stalk, and the HAs of most flu viruses have a similar shape. Similar but not identical. In order to avoid immune attack, HA is continually changing its appearance to the immune system, which is the reason we need to make new seasonal flu vaccines every year or two. There are four different exposed areas on the HA head that are attacked by antibodies, and one of them, called Sa, is pretty much the same in the 1918 virus and its progeny, up to the 1940s or so, and different from the same small area in the seasonal flu viruses prevalent since 1977. This is not the only difference. The post 1977 seasonal H1N1 viruses, unlike the closer to 1918 H1N1 viruses prior to 1957, have host-derived sugars hanging around the same area that shield the underlying protein. That doesn’t mean that we can’t protect ourselves against them, but it does mean that we have to make a different antibody to do it, one that protects us against the post 1977 H1N1 but not the 1918-like HA more characteristic of H1N1s prior to 1957.
The interesting thing revealed by these two papers is that the 2009 swine-derived virus has an HA Sa region very similar to the 1918 virus and in addition has no shielding sugars. This explains lack of cross-reactivity with seasonal vaccines, explains why people who got the 1976 infamous swine-flu vaccine (44 million people) likely have some cross-protection against 2009 swine flu and why us older folks, born in the 1940s do, too. So that’s the story as it appears now. Again, more details in the links above. But there is one additional observation I’d like to make that doesn’t appear in those accounts.
At the outset of this pandemic the statement that the receptor binding domain of the 2009 swine flu virus was extremely close to the 1918 Spanish Flu virus would have sounded ominous. But infectivity, transmissibility and virulence are different things and require different properties. A virus can be just like the 1918 virus “on the outside” but still not a nasty actor “on the inside.” What’s the difference? We can’t say with any definiteness, yet. It’s still one of the big mysteries of influenza. But we’re getting there, and I have no doubt that we will learn yet more in the wake of this pandemic.
Pandemics are bad and they kill people. A lot of people. It would be better not to have to suffer them. But we can still learn a lot from them, if we invest the time, effort and resources.