It has been over thirty years since the discovery of HIV-1
as the virus responsible for AIDS. It
has been a long-standing goal to produce a vaccine able to induce cross-reactive
antibodies that are capable of neutralizing the infectious capability of the HIV-1
virus in all its variant forms. Progress
in this direction has been impeded due to the complexity of the surface
envelope glycoprotein (ENV) – a glycoprotein is a class of proteins containing
carbohydrate moieties. ENV is
responsible for the process that allows the entry of the HIV-1 virus into its
host cell (CD4+ T Helper cells).
ENV is trimer consisting of three glycoproteins with a
molecular weight of 160K. This trimer is
split into a 120K surface component and a 41K membrane component. Together they constitute a moiety that
facilitates the entry of the virus into the host cell called the viral spike. Although the components of the viral spike have
long been considered candidates for a vaccine, it has been elusive. In addition, the viral genes for these
components have been discovered and used in vaccine production; this approach
has also been shown to be unsatisfactory.
The reason for this failure seems to reside in the fact that many of the
regions of the molecular structure of the ENV subunits that are candidates for
eliciting a significant immune response lie buried in areas that are
effectively hidden from immune-surveillance.
As a consequence, investigators have proposed using the
entire ENV trimer as an immunogen – a substance capable of stimulating the
immune system to produce humoral antibodies against it. Unfortunately, the stability of ENV outside
the environment of the viral membrane rapidly degrades. However, this intrinsic difficult has been
effectively sidestepped by R.W Sanders and associates (Science 349,
aac4223(2015)). They overcame this
obstacle by engineering a molecule with covalent disulfide bonds that held the
subunits together. They subsequently
used this modified ENV to immunize rabbits and monkeys. Although it worked effectively against the
same strain of virus from which the ENV was obtained, it was ineffective against
heterologous strains of the deadly virus.
Although the problem of creating an effective vaccine
against HIV-1 remains intractable, future efforts and innovative approaches
similar to ones reported here may finally yield a viable solution. Progress in science necessarily depends on
all the work that has gone on before and the collaborative effort and energy of
many.
