Biology Reference
In-Depth Information
seronegative volunteers vaccinated with a combination vaccination regimen
involving di¨erent viral envelops (Corey et al., 1998) and even cross-clade CTL
activities following vaccination ( Ferrari et al., 1997).
It is generally believed that live attenuated vaccines will o¨er the best hope
for inducing CTL ( Bangham and Phillips, 1997). However, this is risky for
several reasons, particularly the fear that attenuated HIV might not be safe
enough. The next best approach has been the use of other recombinant viruses
that can produce HIV gene products but with lower chance of causing mor-
bidity or mortality in humans ( Rolph and Ramshaw, 1997). So far, vectors
such as attenuated vaccinia viruses, alpha viruses such as Venezuela equine
encephalitis virus ( VEE), and pox viruses are being used (Gorse et al., 1999).
There is insu½cient data to conclude whether CTL must play a role in these
vaccines. Other approaches used include the development of DNA vaccines,
live attenuated bacterial vaccines, immunostimulatory complexes, otherwise
known as ISCOMS, and, to some extent, development of liposomal delivery
systems that deliver soluble antigens for processing and incorporation into the
MHC class I/peptide complex. None of these methods has so far yielded any
data regarding the role of CTL in disease prevention.
CROSS-CLADE HIV-SPECIFIC CTL
One of the most remarkable e¨ects of HIV infection is the viral diversity seen
within and between people, places, and regions, which has raised some skepti-
cism about ®nding a globally e¨ective vaccine. Recent ®ndings by our lab and
others have however shown that HIV-speci®c CTL directed against one clade
of the virus can actually kill viruses of other clades (Betts et al., 1997; Buseyne
et al., 1998b; Jolly et al., 1992). In our study, for example, we examined HIV-
speci®c CTL activity of eight Zambian subjects infected with a clade C virus as
con®rmed by heteroduplex analysis and partial sequence analysis of env and
gag genes. Six out of the eight individuals studied showed strong CTL activity
against recombinant vaccinia virus-infected targets expressing HIV Gag, Pol,
and Env proteins derived from clade B HIV-1 ( IIIB). Other labs have found
similar results. Another interesting ®nding is the presence of shared epitopes
between HIV-1 and HIV-2, which is less aggressive than HIV-1 and less wide-
spread but more predominant in some parts of the world ( Nixon et al., 1990).
This might give hope for a possible pan-HIV vaccine. Some of these epitopes
are also shared between individuals with di¨erent HLA subtypes ( Lynch et al.,
1998).
TREATMENT AND CTL DYNAMICS
Several antiretroviral drugs have been developed over the last decade. Whereas
most of the earlier drugs used in monotherapy have been minimally e¨ective,
the use of combination drug therapy has proven to be very e¨ective. Highly
