[Email to Mary Lou Clements from Bruce Weniger]

Slide 6.
Overinterpretation of data; Unrealistic expectations
o Laboratory assays have no validation
o "Breakthroughs" are expected
o Endpoints
o Prevent initial infection ("sterilizing immunity")
o Prevent or delay AIDS
o Reduce contagiousness
For two long years since planned efficacy
trials of gpl20 were shelved in the United States,
some defenders of that decision have been
criticizing these vaccines. Some say they won't
work because they don't induce cytotoxic T-cells,
or because they don't neutralize certain virus types.
Such criticisms are based on unvalidated
assumptions. The significance and sensitivity of
neutralization assays and cytotoxic T-cell responses
remain unknown for their relevance to human
disease and protection. These assays have to be
validated against protection in humans: "That's
what the efficacy trial will tell you!"
Obviously, it would not make much sense to
pursue a vaccine design that elicited no detectable
immune response of any kind. But the current and
anticipated vaccine candidates do so in one respect
or another. We just don't know what it might take
to tip the balance in favor of the immune system
during critical primary infection.
Other criticism arises because high-risk
vaccine recipients became infected in phase II
immunogenicity trials. These so-called
"breakthrough" patients are entirely to be expected
from a less-than-perfect vaccine. No successful
vaccine in the world today achieves 100%
perfection. Some are overinterpreting what a phase
II trial can reveal, since such studies are too small
and not properly controlled to offer any reliable
estimate of efficacy.
Finally, the assumption that a vaccine must
prevent initial infection with HIV -- so-called
sterilizing immunity (point to bullet) -- is unrealistic
and ignores the state of vaccine science.
Slide 7.
Photo: Dr. Thomas Francis, Jr.
This man directed the largest vaccine field
efficacy trial in medical history. Over 400,000
subjects received the vaccine, and countless
thousands of them experienced "breakthrough"
infections. But the vaccine was a great success.
This is Dr. Thomas Francis, Jr., and the trial was,
of course, for the Salk polio vaccine. Paralytic
disease was averted with 80-90% efficacy, but the
vaccine did not stop the poliovirus from replicating
in the vaccinees. And this is true for nearly all the
vaccines in the world today.
Slide 8.
Graph: Hepatitis B Trial "Breakthroughs"
This principle that successful vaccines permit
breakthrough infections to occur is illustrated by
the phase III hepatitis B vaccine efficacy trials,
shown here.
The bottom graph shows the sizable number
of vaccinees with serologically-detectable hepatitis,

shown in red, or subclinical infection, shown in
blue and green. Hepatitis vaccine had a 92%
efficacy in preventing acute hepatitis, but only
about 54% in preventing infection.
Thank goodness the developers of this vaccine
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