[Email to Mary Lou Clements from Bruce Weniger]

in infected vaccinated subjects. This study was not designed as a study
to compare the virologic or immunologic course of infection in vaccinees
and controls; thus, the ratio of vaccinees to controls was greater than
13:1 and for some trials (with vaccinia recombinants), there were no
controls to study. Thus, his interpretation of the data from humans is
flawed because of inadequate numbers of controls who were infected at
the same time and with similar viruses from the same study populations.
Also, since some subjects received antiviral treatment, we cannot be sure
the virologic data are not confounded.
ABSENCE OF NEUTRALIZING
ANTIBODIES IN VACCINEES:
John will use the AVEG/CHIP joint 401 protocol and the immunology
data from the ADARC to characterize current rgpl20 candidates as
having biologically irrelevant immunogenicity. He will highlight the
absence of cross neutralization as solid evidence that they will not work.
SCIENTIFIC RESPONSES TO HIS ARGUMENTS:
o cross neuts absent may be artifact of insensitive assays;
o successful chimp challenge experiments suggest that antibodies
may do the trick: after all, they achieved a gold standard:
sterilizing immunity.
o modulation of acute infection may be as important for transmission
reduction as prevention of infection altogether, etc.
JOHN MOORE WILL MAKE THE POINT
THAT MONOMERIC GPl20 ARE USELESS,
VERSUS OLIGOMERIC GPI20/GPI60:
Curiously, the prime-boost trial "announced" by Tony Fauci
would use a monomeric vaccine as the Boost.
MOORE'S "PREDICTION" THAT ANIMALS
IMMUNIZED WITH MONOMERIC VACCINES
(WHICH DO NOT INDUCE ANTIBODIES
CAPABLE OF NEUTRALIZING FIELD ISOLATES)
WILL NOT BE PROTECTED FROM A FIELD
ISOLATE CHALLENGE:
Proved to be wrong! (Genentech and Biocine experiments showing
that chimps immunised with MN or SF2 were protected from the SF2
"clinical" isolate). So, beware of making too many predictions based on
isolated laboratory results.
Also (and you made the point) very often our ability to find a
given immune response is limited by the techniques we used (i.e., the
resting cell assay probably made previous neutralization tests irrelevant).
Likewise, tests designed to detect CTLs are still very primitive. CTLs
may be there, but we can not detect them.
NO MONEY FOR TRIALS:
Money should not be the problem. The amount of money that
Brazil wi-l spend this year in antiviral drugs (approx US$ 117 millions)
is the same that the funds that NIH will use for vaccine research.
Obviously there is something wrong there. Money used on vaccine
research is an investment... Money used on drugs is an expense (some
people could even say that is a waste, considering the cost/benefit).
MALARIA VACCINE:
Malaria is like HIV: variable antigens, major public health
morbidity and mortality, immunity not well understood. But there has
been a willingness to put these vaccines into trials. In the Gambia, spf66
malaria vaccine efficacy was about 3%. The same vaccine in Tanzania
showed 15-31% effectiveness. This is better than nothing. We have
much to learn, but that has not prevented us from going to trials.
ONE ARGUMENT HEARD:
Do not move forward with vaccine trials because "the science is

not there yet". I typically counter with the question: what EXACTLY
do you want to know before proceeding?
defining the correlate of immune protection?
getting a better animal model?
understanding the relationship between genotype and immunotype?
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