Let's examine, for a moment, why sequence stability in a pandemic virus is a matter of public concern.
95% Amino Acid Instability + 5% Silent Nucleotide Instability = 100% Overall Instability
Antibody response via the adaptive arm of immunity is developed in the human body against specific amino acid sequences found on a pathogen, e.g. influenza. A viral reservoir continually attempts to escape the host-developed antibody pool by self-revising these defining amino acid sequences. Some reservoirs are more aggressive than others in these self-revisions.
An aggressively revising viral reservoir may effectively escape host antibodies, the mode of defense developed in challenge to a vaccine and / or natural infection, if the pathogen's amino acid changes are widespread, frequent and / or situated in particular areas of the gene code. At this point, all should be aware of individuals who have contracted influenza multiple times, some after having been vaccinated. In these instances, a potential explanation lies in this reservoir's enhanced genetic acquisition cycle.
We continue to evaluate known epitope domains and the surrounding areas in an effort to quantify the potential for immune and / or vaccine escape in this pandemic.
The ΣPF11 reservoir (pH1N1) exceeded the 75% threshold for Amino Acid Instability in a critical HA range with a deposit from the Istituto Nazionale Malattie Infettive 'L. Spallanzani' in Rome. A/Rome/676/2009, a partial sequence from a 39 year old female sampled on 2009-10-28, carries 242E encoded by a first base revision from aAA to create gAA. Several animal flu serotypes (avian/equine) carry the first base change required to build this novel pandemic 242E, including H2N3, H3N8, H5N1 and the H11 series. Zoonotic changes are now common in this reservoir.
The HA of the Rome676 sequence also carries a rare synonymous 190D revision (GAt) found a total of 10 times in the entire GenBank pandemic database and concentrated in Italy (6) with limited presence in the Ukraine, the United States and Afghanistan. This 1918 polymorphism has been conserved on record in swine since at least 1931, was found in the 1976 zoonosis of H1N1 and was carried in the 2005 human seasonal H1N1 (Thai271_S5).
As we have previously reported, 100% of the Hemagglutinin positions between 186 and 248, including antigenic areas of the Receptor Binding Domain (RBD/RBS), are on record as polymorphic. No position in that range is stable. Many positions rate multiple changes. Protein revision is documented at 60 of the 63 positions (95%), engaging the potential for antibody resistance (natural immune escape and vaccine escape).
The viral reservoir backing this present H1N1 flu pandemic is far from stable and is actively acquiring new genetics. Current data does not indicate an immediate direction toward stability.
A complete version with the polymorphisms denoted may be referenced for verification. Please review details on the causality behind this particular study in the earliest version.
Details and Previous Study on this Topic:
- 2010-05-09 pH1N1 Demonstrates 95% Instability In Critical Genetics Range with Extensive Bird Flu Inclusions
- 2010-05-05 90% Change Rate on Unstable HA Antigen Range with H9N2 and H5N1 Bird Flu Matches
- 2010-03-31 Zoonotic H9N2 Avian Influenza Further Destabilises H1N1 Pandemic Genetics
