Lunch for Hungry Minds: A Novel Model for In Vivo SIV Neutralization

• University City Science Center

The holy grail of HIV vaccine development is an immunogen that
elicits antibodies which broadly neutralize field strains of the virus.
While tremendous insights have been gained into the structure and
function of the HIV envelope glycoprotein, precious little progress
has been made in designing such immunogens. In fact, it remains
formally possible that with current technologies, engagement of
the adaptive immune system will not lead to an effective HIV
vaccine. Considering this possibility, we have taken a markedly
different approach to the generation of serum neutralizing activity
against HIV that we have dubbed “reverse immunization.” In this
model, we pre-select the antibody or antibody-like molecule of
interest (i.e, one that broadly neutralizes) then synthetically derive
the representative gene and place it into the context of an adenoassociated
virus (AAV) gene transfer vector. When injected
intramuscularly into a vaccinee, the AAV vector genome directs in
vivo production of the gene product that leads to serum
neutralizing activity against HIV. Recently, we have refined this
approach for the SIV model system, and can now provide in a
single dose, sterilizing immunity to vaccinated monkeys against a
virulent SIV challenge virus. Thus, reverse immunization holds
significant promise as a “designer” approach to an effective HIV
vaccine.