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We have been taught that it's difficult to make vaccines to influenza, HIV and HCV because they lack the proofreading mechanism, hence have high mutation rates. But most RNA viruses and retroviruses are still antigenically stable, such as measles, rabies, polio, yellow fever, HBV etc. So why do only a few viruses successfully become variable? Is it because their receptors allow flexibility, or their glycoproteins have sophisticated conformations that allow more mutations?

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The high mutation rate is only a small part of the reason it's hard to make vaccines against those RNA viruses. The real problem is not that they mutate rapidly, but that they can tolerate high levels of variation in their antigenic regions without losing fitness. Viruses like polio and measles, as you say, have mutation rates easily on a par with influenza or HIV, but when they mutate antigenically significant regions, those new viruses are much less capable of infecting and transmitting between hosts. Vaccines therefore either block the virus replication altogether, or force them into a much weaker form that is much less infectious.

Why do some viruses tolerate antigenic changes better than others? It's not known, but presumably there has been selection for it in those lineages.

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  • $\begingroup$ I can't give an upvote because I am new to here. Your answer is right. $\endgroup$ – Ballistics Jun 6 '16 at 16:57
  • $\begingroup$ It seems that influenza and HIV have employed some sophisticated mechanisms of immune evasion(I don't know the case of HCV). For example, they use a pocket like structure to protect their vulnerable parts. But these are just guesses. $\endgroup$ – Ballistics Jun 6 '16 at 17:05
  • $\begingroup$ Every single modern virus has an array of sophisticated immune evasion mechanisms, being the descendant of a billion years' worth of ancestors that successfully evaded increasingly-sophisticated immune systems. Influenza and HCV are not particularly noteworthy in this respect. $\endgroup$ – iayork Jun 6 '16 at 17:08
  • $\begingroup$ I see, thanks. BTW, can you give me some "noteworthy" examples of the viruses sophisticated at immune evasion? I shall read about them. $\endgroup$ – Ballistics Jun 6 '16 at 17:21
  • $\begingroup$ The most sophisticated at immune evasion are probably the herpesviruses and poxviruses, large DNA viruses that encode multiple genes specifically targeting the immune system. Here and here are starting points $\endgroup$ – iayork Jun 6 '16 at 17:53

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