Understanding Structural Characteristic of Virus Neutralization to Develop Universal Vaccine for Influenza

Deal with the flu is tricky because the virus keep changing its surface proteins by genetic reassortment or drift. Influenza Vaccine made last year might not effective anymore today. That’s why that human can be infected over and over again during the lifetime. This is become a challenges for us to develop what so called “Universal Vaccine for Influenza”.

Now, the big question is how we are going to do that?

One way is by understanding the structural characteristic of human immune system. That is, at least now I understand why it is important to understand the very detail of anatomy and function of antibodies. So, let me step into the detail of it by put what we have learned so far from our class into the context of influenza case.

So far, we have learn that antibody have hypervariable region called Vl (for the light chain) and Vh (for the heavy chain). There are also CDR (Complementary Determining Region) which determine the specificity of each antibody to antigen. We believe also that the antibody have million preexisting “types” to anticipate whatever kind of pathogen molecular structures. But perhaps that won’t works for influenza viruses?

There are 16 antigenically different HA subtypes and 9 antigenically different NA subtypes of influenza viruses. The combination of these two components define all known existing subtypes of Influenza A viruses.

Now, the problem is how our antibody system could provide a rather broad strain protection, than only targeting the HA surface antigen of the viruses, which capable for changing rapidly to avoid and escape from our immune system.

One way to study how our immune system can protect us is to study the how antibody that the survivor of a novel influenza infected person works on preventing from fatal condition.

There is a clue that the antibody of the survivor have a broad protection of flu viruses which might involve a specific region HA2 which is located at the stem or stalk of the HA protein, not at the head!. The HA1 region at the head is believe as a decoy for influenza viruses to escape from neutralization. So, it is suggested that vaccine developer should re-focus on Broad Neutralizing Antibodies (BnAb) that targeting hydrophobic stem region of HA2 and inhibit fusion process, which showed to be cross reactive for multiple viruses, rather then focus on antibody that works on HA1 epitopes. Do you believe that?

Reference:

Han, T. and W. A. Marasco "Structural basis of influenza virus neutralization." Ann N Y Acad Sci. 2011 Jan, 1217: 178-90.

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