Other Vaccines in the Pipeline
Excerpt from
gmhc.org
Among other HIV vaccine candidates, Pasteur-Merieux Connaught's
ALVAC-HIV is closest to human efficacy trials. The vaccine consists
of a collection of HIV genes packed into the canarypox virus, which
infects but does not cause disease in humans. Phase II studies
of this vaccine have shown it can induce cellular responses in 40%
to 60% of vaccinees, although these responses are not long-lasting.
This vaccine is then combined with a "booster," which can be rgp120
or rgp160, to induce the other arm of the immune system,
antibody production. Combining both sets of immune responses,
the cellular and the humoral (antibodies), may create a more complete
immune response that targets HIV-infected cells and free virus,
increasing the potential for successful immunization.
In fact, this vaccine was almost ready to move to efficacy studies,
but the company decided not to go ahead with the current version or
construct, which is called vCP205. It is currently developing newer
constructs that might induce stronger and more diverse cellular
responses. Phase I studies of some of these constructs have started
in France and the United States. Efficacy studies are not planned
until at least the year 2000.
A phase I study of the original vCP205 product is due to start in
Uganda this year, making it the first HIV vaccine to be tested in
Africa. The objective of the Ugandan study is to evaluate the nature
of the CTL immune responses generated by the vaccine.
Most HIV-positive Ugandans are infected with HIV subtypes A and D,
while the product being tested only includes genes encoding for
subtype B core proteins. But there are data from vaccinated
individuals suggesting CTL immune responses against HIV
subtypes A, E and C are being induced in some participants by the
subtype B-based vaccine. Pasteur-Merieux Connaught is also developing
a new generation of canarypox constructs based on HIV subtypes
found in Uganda and elsewhere in Africa.
[...]
Still, these increased efforts face daunting challenges. One of these
is the unwillingness of large pharmaceutical companies to invest in
HIV vaccine development. Pasteur-Merieux Connaught's HIV vaccine
development program stands alone as the only comprehensive program
of its kind among these large corporations. Merck is devoting
increasing resources to its DNA-based vaccine research
(see chart on page 4). Wyeth-Lederle is collaborating with Apollon
on DNA vaccine development. But other traditional vaccine
manufacturers such as SmithKline Beecham have an extremely limited
involvement in the development of vaccines for HIV. Several
potentially viable HIV vaccine candidates have been languishing
in preclinical and phase I limbo due to lack of industry enthusiasm.
It remains to be seen what will be NIH's success in advancing newer
vaccine concepts, and what they can do to boost industry development
of HIV vaccines. |
