Viruses Are Cool #7
Click here to read the introduction to this series.
Influenza virus needs no introduction. Each year, 3-5 million people worldwide experience the misery of severe flu illness and 250,000-500,000 die from it. And this is just for a "normal" flu season--the Asian flu (1957-1958) and Hong Kong flu (1968-1969) pandemics each killed approximately 1 million, and the Spanish flu pandemic of 1918-1919 killed an estimated 40 million.
Currently, there are influenza vaccines which confer protection against disease by inducing an antibody response to two viral surface glycoproteins, hemagglutinin and neuraminidase. Antibody recognition of these two glycoproteins are used to classify influenza viruses into different serotypes. For example, the lethal "H5N1" avian flu strain refers to hemagglutinin serotype 5 and neuraminidase serotype 1.
But there is a problem with these vaccines: hemagglutinin and neuraminidase can undergo changes by spontaneous mutation or by gene reassortment with animal influenza strains, resulting in the frequent generation of new strains to which the human population is not immune. Thus, last year's flu shot, which protected you against last year's flu strains, will do you no good this year because the antibodies generated from last year's vaccine cannot recognize the new "versions" of hemagglutinin and neuraminidase.
The public health strategy, therefore, has been for the WHO's Global Influenza Surveillance Network to monitor circulating influenza virus strains each year, and to recommend a combination of the three most virulent strains in circulation to be used in that year's vaccine. It's a bit like trying to catch a master of disguise by putting up wanted posters featuring the three disguises one believes he is most likely to use--highly effective when one guesses correctly, but not so effective when one guesses poorly.
A recent article, however, reports that a universal vaccine which may protect against all influenza strains is in development. The vaccine involves immunization against the influenza virus M2 protein, which is largely invariant across influenza strains. This strategy is based on previously published work showing that immunization with M2 protects mice from subsequent lethal challenge with both homologous and heterologous influenza strains (Nat Med 5:1157-1163). The study also showed that passive transfer of serum from immunized mice to naive mice protects the latter from lethal challenge, indicating that the protection is mediated by anti-M2 antibodies.
In its latest news release, the company developing the universal flu vaccine reports that the vaccine is safe in human clinical trials and that 90% of subjects given the M2 vaccine plus adjuvant develop antibodies to the vaccine, although whether these antibodies are protective against infection remains to be seen. Another concern is whether M2 will remain invariant in the virus population if this vaccine were widely used. At least one study has suggested that the invariance of M2 is due to its poor immunogenicity during infection. The same study also showed that viral escape mutants with changes in M2 emerge in 65% of infected mice treated with anti-M2 antibodies, but not in mice treated with a control antibody (J Virol 79:6644-6654). This suggests that immunization of humans against M2 could create selective pressure for mutation of the protein, which would bring us right back to where we started.
Nonetheless, these data are encouraging and we can all hope that sometime in the near future, a single flu shot will last us for life.
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4 comments:
Great post! I really should start writing science posts again myself!
I'd read this story somewhere (BBC I think) and I'd also wondered about introducing selective pressure on the antigen that's targeted by the vaccine. I don't know much about immunisation - would pre-existing immunity against the virus be as strong a selective pressure as, say, an antibiotic would be against bacteria? I'm thinking that if the infection can't even get started then there might not be enough rounds of viral replication for new mutations to appear very often, whereas antibiotics are usually introduced once the infection is already established and replication is in full swing.
I wonder if there are any studies out there that looked at emerging resistance to vaccines against other viruses?
Wow, Mad Hatter, thanks for that cool post! And also I appreciate that you wrote it in such a way that I, a layman, could understand it. :)
The flu is fascinating isn't it? I continually come up against the idea that AK natives are immune to bird flu because of the 1980 flu which wiped out many Alaskan villages. I have a hard time explaining to these people why it doesn't work this way.
VWXYNot?--Thanks! I'm no expert on immunization either, but viruses might be able to replicate for a few cycles in some immunized individuals. It's entirely possible people who have had the flu shot still get infected at a cellular level, but the infection is subclinical or asymptomatic. And for the small RNA viruses, one round of replication may be enough to produce a huge viral mutant repertoire.
Also, within a population, there may be people who are not immunized or who have waning immunity in whom viral mutants are generated. Although these mutants may not have an advantage in the non-immunized host, they could be selected for in the population by their ability to infect the people who are immunized.
Arduous--I always worry about using too much science jargon, so I'm really glad you liked it!
Wayfarer--I'm a little confused. Do you mean that they think AK natives are now immune because all the people who were susceptible were killed in the last epidemic?
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