Baltimore and Vaccines
Nobel Laureate David Baltimore presented his findings at the Lou Siminovitch Lecture in Toronto and gave a glimpse of all the recent findings related to the plethora of antibodies that are known to bind to HIV. Many of these have broad specificities and high affinities. It is a fun time for antibody research considering the advances made in deciphering the crystal structure of the viral glycoprotein.
Baltimore introduced the work of his lab, particularly that of Alex Balazs, in developing a novel form of therapeutics. Termed "Vectored ImmunoProphylaxis" or VIP, the concept is that of getting the body to make antibodies against the virus.
Basically, Baltimore and Balazs engineered an Adeno-associated Virus (AAV) which has a small genome to express the heavy and light chains of their favourite antibody. This could be against HIV, Hepatitis or Malaria. The virus is injected into the muscle of mice where the vector starts expressing the antibody protein. When the mouse is challenged with the pathogen, the antibodies that are produced in the muscle now enter the plasma and neutralize the pathogen. This was effectively shown for several pathogens and their paper was published in Nature Medicine in Oct 2014.
It is fascinating to know that
1. The muscle can produce antibodies
2. The foreign antibodies can comprise unto 10% of the host antibodies without any adverse effects.
3. This tool can be used against any pathogen.
4. Using a Cre-Lox system, the antibody gene can be excised if the host does not need the protein to be expressed anymore.
There are several issues
1. This is a form of gene therapy and has its own risks, even though AAV is a safe viral vector.
2. The size of the vector is limited which reduces the capacity of the vector to incorporate transgenes.
2. That a mouse muscle can produce tons of antibodies without any adverse long term effects is easier said than done.
Baltimore introduced the work of his lab, particularly that of Alex Balazs, in developing a novel form of therapeutics. Termed "Vectored ImmunoProphylaxis" or VIP, the concept is that of getting the body to make antibodies against the virus.
Basically, Baltimore and Balazs engineered an Adeno-associated Virus (AAV) which has a small genome to express the heavy and light chains of their favourite antibody. This could be against HIV, Hepatitis or Malaria. The virus is injected into the muscle of mice where the vector starts expressing the antibody protein. When the mouse is challenged with the pathogen, the antibodies that are produced in the muscle now enter the plasma and neutralize the pathogen. This was effectively shown for several pathogens and their paper was published in Nature Medicine in Oct 2014.
It is fascinating to know that
1. The muscle can produce antibodies
2. The foreign antibodies can comprise unto 10% of the host antibodies without any adverse effects.
3. This tool can be used against any pathogen.
4. Using a Cre-Lox system, the antibody gene can be excised if the host does not need the protein to be expressed anymore.
There are several issues
1. This is a form of gene therapy and has its own risks, even though AAV is a safe viral vector.
2. The size of the vector is limited which reduces the capacity of the vector to incorporate transgenes.
2. That a mouse muscle can produce tons of antibodies without any adverse long term effects is easier said than done.
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