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International Society for Infectious Diseases
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Date: Sun 14 Apr 2013
From: Anne DeGroot
Scientists at EpiVax performed an extremely rapid bioinformatics analysis on the genome sequences of H7N9 influenza and predict that it will be difficult to make effective vaccines and low cost diagnostics for the newly emerging virus (also called H7N9/A/Shanghai/1/2013), meaning that the new H7N9 may be a "stealth" virus that is able to fly under the immune system's radar. And, they predict, should the H7N9 "stealth virus" adapt itself for human-to-human transmission, it has serious potential for rapid expansion on a global scale.
What makes the new flu invisible to the immune system? The protein that is usually incorporated in vaccines known as HA (hemagglutinin) has fewer immune-stimulating "T cell epitopes" than many previously circulating strains of flu (see image at http://www.epivax.com/wp-content/uploads/2013/04/H7N9_Immunogenicity_EpIVax_12Apr13_AGM1.jpg).
The analysis done by the EpiVax team of expert vaccine designers is consistent with reports that previous H7 vaccines also had low immunogenicity. Last season's [2011-2012] H3N2 was also predicted by EpiVax to be low immunogenicity, and epidemiological evidence of outbreaks among H3N2-vaccinated individuals confirms the prediction. Unless it is engineered for higher immunogenicity, a vaccine against H7N2 may have similar low efficacy as was seen with H3N2.
Low T cell epitope content generally means that it is harder to make high-affinity antibodies, the type that protect against flu and that are used to make low-cost diagnostic tests like ELISAs. While one rapid test for flu (based on PCR) is available, lacking a low cost rapid test, it could be harder to screen the expanding numbers of individuals that have already been exposed to active H7N9 cases. More than 1000 such cases are being "followed" by Chinese health authorities.
The EpiVax scientists did a similar analysis of pandemic H1N1 in 2009 [1] and correctly predicted that pandemic H1N1 would not cause severe disease in most individuals, a prediction that was subsequently validated in vitro and in vivo by many others. Unfortunately, the immunogenicity news is not so good for H7N9.
Detailed information with references/publications can be found athttp://bit.ly/H7N9EpiVax.
[1] Previous publication demonstrating cross-conservation between seasonal influenza and H1N1 published during 2009 pandemic: De Groot AS, Ardito M, McClaine EM, Moise L, Martin WD. Vaccine. 2009 Sep 25; 27(42):5740-7. doi: 10.1016/j.vaccine.2009.07.040. Epub 2009 Aug 4. Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine.
--
Anne S. De Groot, MD
Professor and Director, Institute for Immunology and Informatics
University of Rhode Island
and
CEO/CSO EpiVax
http://www.EpiVax.com
[ProMED-mail thanks Professor De Groot for making the EpiVax bioinformatics analysis of the genome sequence available for our readers.
The conclusions of the analysis are in line with previous predictions that the path to development of an effective vaccine may be slow and problematic. Fortunately, hemagglutinin inhibitors are treatment options in the interim. The EpiVax interpretation that the avian H7N9 influenza virus has the properties of a "stealth virus" is novel and in line with current knowledge of the behaviour of the virus. - Mod.CP
