- 现金
- 281 元
- 精华
- 0
- 帖子
- 65
- 注册时间
- 2002-3-11
- 最后登录
- 2012-6-26
|
5楼
发表于 2002-6-16 10:44
Re:Hope
According to many scientists, vaccines using a logical molecule,
gp120--the protein the virus uses to invade immune cells, as
discussed above--haven't worked, probably because the
antibodies that such vaccines elicit bind to the wrong part of
the molecule. Gp120 shields the precise binding site it uses to
latch onto CD4, its docking site on immune cells, until the last
nanosecond, when it snaps open like a jackknife. One way to get
around this problem, suggested in a paper published in Science
three years ago by Jack H. Nunberg of the University of Montana
and his colleagues, would be to make vaccines of gp120 molecules
that have previously been exposed to CD4 and therefore have
already sprung open. But those results have been "difficult to
replicate," according to Corey, making researchers pessimistic
about the approach.
Another possible hurdle to getting an AIDS vaccine that elicits
effective anti-HIV antibodies is the variety of HIV subtypes,
or clades, that affect different areas of the world. There are
five major clades, designated A through E. Although clade B is
the predominant strain in North America and Europe, most of
sub-Saharan Africa--the hardest-hit region of the globe--has
clade C. The ones primarily responsible for AIDS in South and
Southeast Asia--the second biggest AIDS hot spot--are clades B,
C and E.
Several studies indicate that antibodies that recognize AIDS
viruses from one clade might not bind to viruses from other
clades, suggesting that a vaccine made from the strain found in
the U.S. might not protect people in South Africa, for example.
But scientists disagree about the significance of clade
differences and whether only strains that match the most
prevalent clade in a given area can be tested in countries there.
Essex, who is gearing up to lead phase I tests of a clade C-based
vaccine in Botswana later this year, argues that unless
researchers are sure that a vaccine designed against one clade
can cross-react with viruses from another, they must stick to
testing vaccines that use the clade prevalent in the populations
being studied. Cross-reactivity could occur under ideal
circumstances, but, he says, "unless we know that, it's
important for us to use subtype-specific vaccines."
Using the corresponding clade also avoids the appearance that
people in developing countries are being used as guinea pigs for
testing a vaccine that is designed to work only in the U.S. or
Europe. VaxGen's tests in Thailand are based on a combination
of clades B and E, and in April the International AIDS Vaccine
Initiative expanded tests of a clade A-derived vaccine in Kenya,
where clade A is found.
But in January, Malegapuru William Makgoba and Nandipha Solomon
of the Medical Research Council of South Africa, together with
Timothy Johan Paul Tucker of the South African AIDS Vaccine
Initiative, wrote in the British Medical Journal that the
relevance of HIV subtypes "remains unresolved." They assert that
clades "have assumed a political and national importance, which
could interfere with important international trials of
efficacy."
Early data from the Merck vaccine trials suggest that clade
differences blur when it comes to cellular immunity. At the
retrovirus conference in February, Emini reported that killer
cells from 10 of 13 people who received a vaccine based on clade
B also reacted in laboratory tests to viral proteins from clade
A or C viruses. "There is a potential for a substantial
cross-clade response" in cellular immunity, he says, "but that's
not going to hold true for antibodies." Corey concurs that clade
variation "is likely to play much, much less of a role" for killer
cells than for antibodies because most cytotoxic T cells
recognize parts of HIV that are the same from clade to clade.
Johnston of NIAID theorizes that one answer would be to use all
five major clades in every vaccine. Chiron in Emeryville, Calif.,
is developing a multiclade vaccine, which is in early clinical
trials. Such an approach could be overkill, however, Johnston
says. It could be that proteins from only one clade would be
recognized "and the other proteins would be wasted," she warns.
Whatever the outcome on the clade question, Moore of Weill
Medical College says he and fellow researchers are more hopeful
than they were a few years ago about their eventual ability to
devise an AIDS vaccine that would elicit both killer cells and
antibodies. "The problem is not impossible," he says, "just
extremely difficult."
According to many scientists, vaccines using a logical molecule,
gp120--the protein the virus uses to invade immune cells, as
discussed above--haven't worked, probably because the
antibodies that such vaccines elicit bind to the wrong part of
the molecule. Gp120 shields the precise binding site it uses to
latch onto CD4, its docking site on immune cells, until the last
nanosecond, when it snaps open like a jackknife. One way to get
around this problem, suggested in a paper published in Science
three years ago by Jack H. Nunberg of the University of Montana
and his colleagues, would be to make vaccines of gp120 molecules
that have previously been exposed to CD4 and therefore have
already sprung open. But those results have been "difficult to
replicate," according to Corey, making researchers pessimistic
about the approach.
Another possible hurdle to getting an AIDS vaccine that elicits
effective anti-HIV antibodies is the variety of HIV subtypes,
or clades, that affect different areas of the world. There are
five major clades, designated A through E. Although clade B is
the predominant strain in North America and Europe, most of
sub-Saharan Africa--the hardest-hit region of the globe--has
clade C. The ones primarily responsible for AIDS in South and
Southeast Asia--the second biggest AIDS hot spot--are clades B,
C and E.
Several studies indicate that antibodies that recognize AIDS
viruses from one clade might not bind to viruses from other
clades, suggesting that a vaccine made from the strain found in
the U.S. might not protect people in South Africa, for example.
But scientists disagree about the significance of clade
differences and whether only strains that match the most
prevalent clade in a given area can be tested in countries there.
Essex, who is gearing up to lead phase I tests of a clade C-based
vaccine in Botswana later this year, argues that unless
researchers are sure that a vaccine designed against one clade
can cross-react with viruses from another, they must stick to
testing vaccines that use the clade prevalent in the populations
being studied. Cross-reactivity could occur under ideal
circumstances, but, he says, "unless we know that, it's
important for us to use subtype-specific vaccines."
Using the corresponding clade also avoids the appearance that
people in developing countries are being used as guinea pigs for
testing a vaccine that is designed to work only in the U.S. or
Europe. VaxGen's tests in Thailand are based on a combination
of clades B and E, and in April the International AIDS Vaccine
Initiative expanded tests of a clade A-derived vaccine in Kenya,
where clade A is found.
But in January, Malegapuru William Makgoba and Nandipha Solomon
of the Medical Research Council of South Africa, together with
Timothy Johan Paul Tucker of the South African AIDS Vaccine
Initiative, wrote in the British Medical Journal that the
relevance of HIV subtypes "remains unresolved." They assert that
clades "have assumed a political and national importance, which
could interfere with important international trials of
efficacy."
Early data from the Merck vaccine |
|