Immunotherapy for Infectious Diseases

190 Kalams
Another promising approach toward immune reconstitution will involve the use
of mature, monocyte-derived dendritic cells. These are extremely potent antigenpresenting
cells that have been shown to generate de novo helper immune responses
efficiently, as well as augment memory CTL responses in vivo (124–126). They can be
thought of as nature’s adjuvant and have already been shown to increase the immunogenicity
of Canarypox constructs in HIV-seronegative individuals (127).
Other promising immunogens soon to enter clinical trials include Venezuelan equine
encephalitis virus vectors (128,129), DNA vaccines (130–133), and vaccines based on
adenovirus vectors (134). It has recently been demonstrated that Tat-specific immune
responses are important for the initial containment of SIV replication, so selective augmentation
of these responses might also be beneficial (135).
CONCLUSIONS
With the ability to suppress HIV replication with HAART, and with evidence that
treatment of infected subjects early after infection allows preservation of immune
responses and potential control of HIV replication in the absence of HAART, there is
reason to be optimistic that immune control of HIV infection can be achieved. However,
there are a number of factors that provide potential hurdles for long-term immune
control of HIV, especially in chronically infected persons. With a well-established,
diverse quasispecies firmly entrenched, there may be HIV variants present that are not
recognized by the host’s CTL response, or that contain mutations within CTL epitopes
that diminish binding to HLA class I molecules. In either case, augmentation of CTL
responses with therapies representing consensus sequences may not be effective. However,
it is possible that the ability to stimulate robust helper responses may allow the
immune system to evolve continuously, to recognize new virus variants.
These hurdles make the prospect for immune-mediated control of virus replication challenging.
However, the recent demonstration that immune-mediated control of HIV is possible,
combined with several new constructs now entering clinical trials, provides a strong
rationale to pursue HIV-specific immunotherapy for the treatment of HIV infection.
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