[Email to Mary Lou Clements from Bruce Weniger]

Weniger, Bruce

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Weniger, Bruce [CORP/NIPI/bgw2]
30-Jun-96 13:31
Clements, Mary Lou (JHU)
29Jun Draft (part 2)

CONTINUED FROM PRIOR MESSAGE
Slide 13.
Vaccines Put Into Efficacy Trials Lacking Animal
Vaccines Lacking
Good Animal Models

Models or Immune Correlates
Vaccines lacking Immune
Correlates of Protection

Rotavirus
Salmonella typhi
Pertussis
Malaria
Dengue
Meningococcus
Pneumococcus
Diphtheria
Cholera
Gonorrhea
Hemophilus influenzae B
Argentine hemorrh. fever
Live, atten. influenza

1'
p
P
P
P
P
P
P
P
P

P
P
P
P

P
The history of vaccine development is filled
with examples of other vaccines which were put
into efficacy trials for which there was no good
animal model, or in which there was no serologic
correlate of immune protection, or before we
understood their mechanism of action or the
pathogenesis of the organism. In most cases,
complete success does not occur in the first trials,
but what is learned gives rise to second or third
generation vaccines which have been quite
successful, such as for Hemophilus influenzae B
and rotavirus. Other vaccines have required
decades of dogged work and multiple efficacy
trials.
We still do not know the correlates of
immunity for pertussis disease, but in recent years I
understand the U.S. N.I.H. has poured tens of
millions of dollars into a series of large efficacy
trials of acellular pertussis vaccines in Sweden and
Italy, which have shown these products quite
efficacious.
In some cases, such as malaria and
gonorrhea, a highly-effective vaccine has yet to be
discovered after a number of human efficacy trials.

Slide 14.
Efficacy trials fill critical knowledge gaps
o Protection: Yes or No?
o Serologic correlates of immunity
o "Theorists" vs. "empiricists"
Spier, Vaccine, 1995;13:1487.
o "Failure" is inconclusiveness, not low or no efficacy
A "fear of failure" is operating with AIDS
vaccine efficacy trials (point to last bullet). There is an
unfortunate attitude that there will be but one and
only one opportunity to test an AIDS vaccine for
efficacy. This is a self-defeating attitude which will
111111111111111111 cause years of delay in the incremental steps it
often takes to develop a useful vaccine.
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