Evaluation of H7N9 (Shanghai 2013) for T cell epitopes and cross-reactivity with circulating strains of Influenza (see slides below).
Extremely Rapid H7N9 Vaccine Design by EpiVax
EpiVax performed an extremely rapid analysis of the H7N9 vaccine sequence that is associated with an increasing number of deaths in Shanghai, China. One purpose was to show that we could design a vaccine within 36 hours (we succeeded, please see attachments below). In response to several requests for additional information, we have evaluated the cross-conservation of T cell epitopes between the emerging H7N9 and seasonal strains of influenza.
There is reason for concern at all levels. Not only are human populations unlikely to have cross-reactive antibody epitopes, the lack of conservation of T helper and CTL epitopes in the two most important vaccine antigens (HA and NA) are of great concern.
Thus the purpose of this Blog Post is to update our collaborators on the status of the H7N9 epitope prediction project and to provide an early report of our level of concern.
Question: If H7N9 becomes an influenza epidemic, what is the impact of prior vaccination, or infection with seasonal flu?
Response: Unfortunately, unlike the previous H1N1 pandemic, there is little conservation between the emerging H7N9 pandemic strain and seasonal types of influenza. While there is some very strong conservation between H7N9 internal protein epitopes with epitopes found in Influenza A California H1N1 from 2009, for CLass II and Class I epitopes, these epitopes are never found in HA or NA, the two proteins that are usually produced in the vaccine (the internal proteins are not included, instead, a ‘trojan horse’ strain is used to produce the vaccine in eggs).
Question: How does this compare to the previous H1N1 pandemic situation?
Response: The emerging H7N9 situation is in stark contrast with the situation in 2009, when H1N1 California was the emergent strain, and H1N1 Brisbane was the seasonal strain. At that time (see paper linked here), we examined the exact sequences of the predicted Class II epitope clusters, and found that nine out of sixteen (56%) of the Thelper epitopes within A/California/04/2009 H1N1 HA were 100% conserved with the corresponding sequence in A/Brisbane/59/2007 H1N1. An additional four out of the sixteen (25%) HA epitope clusters were 90% conserved with their corresponding sequences in A/Brisbane/59/2007 H1N1.
Question: What does that mean for human populations – is there a risk of serious disease following infection?
Response: In short – we find LESS conservation than was present during the H1N1 pandemic. We believe that there would be LESS protection than was observed – some believe that H1N1 pandemic influenza did not turn out to be such a bad illness because there was cross-conservation of the epitopes. I have linked that paper below.
Question: Will seasonal influenza vaccination protect against H7N9?
Response: We believe that the Seasonal Flu Vaccine (usually composed of HA/NA but no other proteins) would not protect (there are no cross-conserved epitopes to speak of) but INFECTION with circulating strains of H1N1 (during infection internal proteins are presented to the immune system) might.
We have proposed that officials in China determine whether patients who are sick with H7N9 were VACCINATED but not INFECTED with H1N1.
They could also synthesize the peptides provided in our previous paper, and the ones included in our table, and compare their T cell responses ex vivo to the H1N1 CA T helper epitopes (in the supplemental table attached) with the new H1N1 class II epitopes we just predicted.
If any parties reading this email are interested testing the epitopes we predicted, we can definitely send the sequences. Email Us Here.
Dr. Annie De Groot, MD
CEO/CSO EpiVax, Inc.
- Providence Business News Article on EpiVax
- Recent H7H9 Articles: CDC, Forbes, Forbes 2, LA Times,
Laurie Garrett Interview
- Related Blog Post: http://www.epivax.com/blog/faster-safer-vaccines-for-a-nation-at-risk/
- Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine
- Extremely Rapid H7N9 Vaccine Design – Download deck here.
NEW UPDATED SLIDES BELOW