Biology Reference
In-Depth Information
search for vaccines. Several cohorts of these individuals exist, including men
who have sex with men, intravenous drug users, commercial sex workers, ex-
posed healthcare workers, heterosexual couples in monogamous relationships,
and children born to infected mothers ( Rowland-Jones et al., 1993, 1998b). In
almost all these groups, HIV-speci®c CTL has been shown to exist, although
the nature and signi®cance of these responses di¨er from one study to another.
In a study of exposed seronegative commercial sex workers in Gambia and
Kenya, for example, 6 out of 15 Kenyan and 5 out of 6 Gambian sex workers
showed HIV-speci®c CTL following repeated testing ( Rowland-Jones et al.,
1995). In our study of a cohort of 47 Zambian exposed-uninfected individuals
who are involved in monogamous relationships with HIV-infected individuals,
9 individuals (20%) elicited HIV-speci®c CTL following a single assay using the
chromium release assay. We also found that the presence of HIV-speci®c CTL
in these individuals correlates with high viral load in their corresponding HIV-
infected partners. It is, however, not clear whether these results represent what
actually happens in vivo or whether they de®nitely play a role in preventing
these individuals from getting infected.
CTL IN VACCINE DEVELOPMENT
It is widely believed that the only way to slow down the HIV epidemic is
through the use of an e¨ective vaccine. This view is bolstered by the ®ndings
showing a possible role being played by HIV-speci®c CTL in slowing down the
progression to HIV in several studies. Several candidate vaccines have been
developed and more are in development (Girard et al., 1999; Gorse et al.,
1999). Most of the initial candidate vaccines were based on recombinant en-
velop proteins and were targeted at obtaining neutralizing antibodies to HIV
(Johnston, 1997). The frequent mutations involving the env gene segment and
the several ®ndings that CTL might play a role in control of HIV lead many to
conclude that an e¨ective vaccine must have the capability of eliciting both
humoral and cellular immunity ( Kourilsky et al., 1998). There is a lot of skep-
ticism regarding the ®nding of an e¨ective HIV vaccine because of the high
genetic variation of HIV quasi-species, even within the same individual. It is
believed that any e¨ective vaccine must be able to have polytypic properties
that will cover as many HIV quasi-species as possible (Woodberry et al., 1999).
There is also a concern raised regarding the ability of the virus to enter a
latency stage in some cells thereby escaping the immune system as well as the
need for vaccines that will confer persistent immunity to control the virus. Most
of the current data involving vaccines are from animal studies. Although most
murine and some primate studies have shown mild to strong HIV-speci®c CTL
following immunizations with candidate vaccines, it is unclear whether that will
be the picture in humans.
Using canary pox vaccine, one group has demonstrated the presence of HIV-
speci®c CD8
CTL responses in seronegative volunteers ( Belshe et al., 1998;
Evans et al., 1999). Other studies have shown signi®cant CTL responses of
