Posted: Wed Feb 25, 2009 10:33 am Post subject: Good Explanation of Monoclonal Antibodies and Virus Picture
There are two sections to a virus: The peanut shaped head and the neck (or tail). The head mutates quickly while the neck portion is invariable (does not change).
The monoclonal antibodies attach themselves to the neck of the A-type virus particles and prevent them from changing shape. The viruses are unable to enter the cell if they cannot change shape. "An important goal is to redirect the immune response of vaccines to this invariable region of the hemagglutinin to try to obtain durable lifelong immunity," according to Dr. Marasco, Jianhua Sui, M.D., Ph.D.
By studying tens of billions of monoclonal antibodies produced in bacterial viruses, Dr. Marasco and other Dana-Farber colleagues found 10 antibodies active against the four major strains of H5N1 avian influenza viruses. Three of these antibodies had broader neutralization capabilities against representative strains of other known influenza A viruses.
This means there antibodies were effective against the seasonal H1 viruses, the H1 virus that caused the 1918 pandemic and the highly pathogenic avian H5 subtypes—but none of the viruses containing the six Group 2 HAs.
When they surveyed more than 6,000 available HA genetic sequences of the 16 HA subtypes, they found the pockets to be very similar within each Group but to be significantly different between the two Groups. The genetically stable pockets, they note, may be a result of evolutionary constraints that enable virus-cell fusion. This could also explain why they did not detect so-called escape mutants, viruses that elude the monoclonal antibodies through genetic mutation.
Simultaneously, Dr. Marasco’s group teamed up with Robert C. Liddington, Ph.D., professor and chair of the Infectious and Inflammatory Disease Center at Burnham, to determine the atomic structure of one of their monoclonal antibodies bound to the H5N1 HA. Their detailed picture shows one arm of the antibody inserted into a genetically stable pocket in the neck of the HA protein, an interaction that blocks the shape change required for membrane fusion and virus entry into the cell.
"One of the most remarkable findings of our work is that we identified a highly conserved region in the neck of the influenza hemagglutinin protein to which humans rarely make antibodies," says Dr. Marasco. "We believe this is because the head of the hemagglutinin protein acts as a decoy by constantly undergoing mutation and thereby attracting the immune system to produce antibodies against it rather than against the pocket in the neck of the protein."
You cannot post new topics in this forum You cannot reply to topics in this forum You cannot edit your posts in this forum You cannot delete your posts in this forum You cannot vote in polls in this forum