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A novel swine influenza virus variant has become widespread in swine populations in China since 2016 and has “all the essential hallmarks of a candidate pandemic virus”, according to a recent publication in the journal “Proceedings of the National Academy of Sciences of the US” (PNAS). This swine flu strain has been identified and studied by a team of researchers from the Harbin Veterinary Research Institute, China. They claim that “immediate action is needed to prevent the efficient transmission of this H1N1 swine flu variant to humans”. The PNAS article has received abundant media attention.
Will this virus cause the next pandemic? How worried should we be?
Pig 333 has interviewed Kristien Van Reeth, professor of virology at Ghent University, Belgium, and swine influenza virus expert. She believes these interesting research findings need much more nuance, and tries to put things in perspective.
“What makes the virus remarkable and is it really unique?”
The novel virus belongs to the H1N1 subtype. Like many swine influenza viruses, it is a “reassortant”, a hybrid virus with genetic material from two or more existing viruses. In this case, the surface proteins H1 and N1 come from the “Eurasian avian” H1N1 swine influenza virus. The latter virus has been circulating widely in Europe since 1979 and has later spread to Asian countries. The internal genes and proteins are mainly from the 2009 pandemic H1N1 or “Mexican flu” strain, which was also of swine origin. Only one of these proteins has been derived from a North American swine virus. Similar reassortant viruses were previously found in other places in China, as well as in Europe. Thus, this particular reassortant, which is dubbed G4, is not entirely novel. It is remarkable, though, that reassortants with internal genes from the 2009 pandemic H1N1 virus seem to be on the increase.
“Why does the study conclude that the G4 virus has pandemic potential?”
This conclusion is largely based on experiments in ferrets, a common animal model for humans. G4 viruses readily infected and transmitted between ferrets. But ferrets are not humans, and this does not mean that G4 has the capacity for human to human transmission, which is required to start a pandemic. More important, there are dozens of other swine influenza virus variants that have been shown to transmit between ferrets under experimental conditions. Yet, with the exception of the 2009 pandemic H1N1 virus, none of these has turned into a pandemic strain.
The researchers could not detect any antibodies to the G4 strain in more than 90% of the people studied. G4 thus belongs to the category of swine flu strains for which the human population is largely immunologically naïve. This is another requirement for a pandemic influenza virus. But there are several other swine flu strains for which human population immunity is lacking or very low. In other words, there are insufficient arguments that G4 poses unique public health risks in comparison with other swine flu strains.
“How many humans have become infected with G4?”
About 10% of swine industry workers in China seem to have antibodies against G4. But such antibodies do not necessarily result from exposure to or infection with the swine virus. It is possible that these are “cross-reactive” antibodies due to past infections with human H1N1 strains. Humans encounter numerous influenza virus strains and vaccinations during their lifetime, and the resulting immune memory will influence responses to novel strains. While a single shot of human flu vaccine will not protect against G4, as shown in the PNAS paper, people with complex influenza immune backgrounds may react differently. We need more animal model experiments to understand how subsequent exposures to distinct H1N1 strains will shape the immune response.
It is important to stress that almost all swine influenza virus strains can jump from swine to humans. Each year, there are confirmed human infections with swine flu viruses. These viruses are diagnosed in respiratory specimens and then called “variant” swine flu viruses. Only two such infections with G4 viruses have been demonstrated in China, in 2015 and 2018. There were comparatively more reported cases of human infection with the original avian-like swine H1N1 virus: five cases in China and five in Europe since 2015. Most zoonotic swine flu infections occur in people with close contact with pigs, such as swine farmers, animal caretakers, and visitors of large agricultural fairs in the US. Common hallmarks are a mild clinical picture and a lack of onward person-to-person spread or a “dead end”. The one well known exception is the 2009 pandemic H1N1 influenza virus. This latter virus has donated its internal genes to the current G4 and many other reassortant viruses of swine. Researchers believe that these “pandemic” internal genes may promote adaptation to humans. While the specific genetic traits that make a swine virus transmissible between humans remain obscure, G4 and other swine flu viruses need to be monitored closely.
“What is the opinion of other influenza experts? What can we do about it?”
This Chinese research paper does not come as a surprise to veterinary virologists. It is just another wake-up call that swine flu viruses need to be monitored better, in pigs and also in humans. These viruses come in a variety of antigenic flavors - or clades - and genetic constellations. They change rapidly over time, and they differ in different continents and regions. We need a more complete picture of the dominant strains in swine-dense regions worldwide. Those strains should also be used to compare antibody titers in people of different ages, and in infection and transmission studies in various animal species. This way scientists can identify strains with the highest public health risk. This information is needed for WHO to select and develop candidate swine influenza vaccine strains, and seed stocks to make a human vaccine. This important mechanism is already in place, but the current selection is based on too limited and patchy data.
Veterinarians and swine farmers are at the frontline for diagnosing influenza in pigs and in people, and for providing researchers with the proper samples. We will never be able to predict or prevent pandemics, but the cooperation of swine vets and the swine industry can make a big difference for pandemic preparedness.
