Last week we asked you to think about the pork farmer, knee deep in dead piglets, when you had your bacon and eggs for breakfast. This week, we bring you poultry farmers in China who are trying to make you look the other way.
Chinese poultry producers are battling with the Chinese Centers for Disease Control (CDC) to re-name H7N9 Avian-origin Influenza, so that people will not think of Chickens when they think of Flu. There’s a great blog on CIDRAP that talks about the many reasons why it’s a really, really bad idea to try to obscure the truth when it comes to disease outbreaks. Read it here.
So what’s really going on over there?
Well, things are not looking good. In various regions of China (particularly agricultural regions surrounding big cities like Shanghai and Hong Kong), the number of cases has ticked upwards since the beginning of the year, and we’re now at more than 310 cases – in a very much shorter period of time than it took H5N1 to get to this level. (Great graphic from Ian Mackay, Virology Down Under, here:
The biggest worry, from our perspective, is vaccine efficacy. The immunogenicity of the H7N9 produced using standard approaches, or cell-culture methodology, is abysmal. We predicted that (see the original blog about H7N9, the ‘stealth virus’, here), but that is little comfort when it comes to designing vaccines that will stop this very worrisome, and expanding, emerging infectious disease.
In fact, the Novartis vaccine company recently reported that H7N9 cell culture-produced vaccine without adjuvant produced extremely low seroconversion rates of 6%. In contrast, the rate of seroconversion to unadjuvanted monovalent pandemic H1N1 was 89% in one study (Plos One Griffin MR et al. 2011 Aug 6(8)). Rates of seroconversion to trivalent seasonal vaccine are 84% on average to the three strains of virus in the vaccine. (Goodwin et al. 2006(24):1159-1169; CDC MMWR September 20, 2013/ 62(RR07).
But to every yin, there’s a yang, so to speak. We can learn a lot from H7N9 itself, and the epidemic, when it comes to making biologics that are equally non-immunogenic. Take for example the following three aspects of the new H7N9 and apply them to your favorite (immunogenic) biologic drug:
(1) T cell epitope content is directly linked to antibody titers. By that we mean – low T cell epitope content (by deleting or deimmunizing proteins) can lead to low antibody titers. For vaccines, bad, but for protein therapeutics, great!
(2) Epitope concentration matters. Doesn’t really matter what else is in the mix, it’s the number of epitopes in the actual target protein that matters. There are a lot of epitopes in other parts of H7N9, but they don’t appear to be helping. It looks as if the number of T cell epitopes in a given protein will make or break the immune response to it. So, for protein therapeutics, you just have to deimmunize or tolerize against the key driver of immunogenicity. Or perhaps, just deimmunize key regions.
(3) Tolerize. We believe H7N9 also has managed to introduce Treg epitopes, or, as we like to call them, Tregitopes. We’ll be talking more about that when our new H7N( paper has shaped up and is accepted for publications. The key finding (viruses appear to alter their sequences so that they are more cross-reactive with the human genome and may even induce Tregs) will be published very, very soon (look for Chris-Bailey Kellog, Andres Guitierrez, and Annie De Groot in Pubmed).
(4) Don’t believe the dogma. But if you did, you wouldn’t be reading this blog. And, for that same reason, you are amazed that big Pharma-Vaccine companies would spend millions making an H7N9 vaccine that we predicted – before they even started work on it – wouldn’t work. Whatever. You’re in the right place – this is where we are “Think out Loud”. And if you’re interested in learning from pathogens how they escape human immune response, so that we can design better vaccines, hang right here (click the link to sign up for our newsletter). More cool stuff forthcoming.