IAVI Report Vo. 5, no. 2

THIRD CONFERENCE
continued from page 7

CpG-containing oligodeoxynucleotides were safe and could
provide immune stimulation.
Clinical trials of a number of candidate HIV vaccines were
also described. A Phase I/II trial of VaxGen's B/E bivalent
gp 120 vaccine showed the expected profile of safety and
immunogenicity as measured by antibodies and neutralization
of MN strains of HIV. In a WRAIR study, Aventis Pasteur's
oligomeric envelope protein (o-gp140) tested alone and in
combination with ALVAC-HIV (vCP205) was safe and showed
some evidence of neutralization against a primary strain of
HIV. The o-gp140 construct was formulated with a novel
adjuvant known as PCPP.
The meeting featured at least two talks on overall vaccine
safety issues. Frederick Miller of the U.S. Food and Drug
Administration (FDA) described collaboration between FDA
and the American College of Rheumatology that will define

criteria for evaluating possible induction of autoimmunity by
vaccination and guide how such reports should be investigated.
This effort could bring some much-needed critical scientific
data to bear on a controversial topic. In addition, John
Petricciani, vice president of the International Association for
Biological Standardization in Geneva, reviewed progress toward
relaxing limits on the use of a broader variety of tissue
cultured cells to produce vaccines. Uncertainty about which
cells may ultimately be acceptable could be a stumbling block
to development of particular vaccine approaches.
Pat Fast is associate director of clinical research at Aviron, a
California-based biotechnology company, and the former
associate director of the Vaccine and Prevention Program at
the US. National Institute of Allergy and Infectious Diseases'
Division of AIDS.

PARIS VACCINE MEETING
continued from page 6

directed mostly at conformational epitopes. Pilot studies using
a prime-boost regimen in monkeys are now underway, together
with Leo Stamatatos of the Aaron Diamond AIDS Research
Center. So far, V2-deleted oligomers (a more immunogenic
form of gp140), but not gp120 monomers, have induced
antibodies that neutralize some primary isolates (including the
standardized panel provided by NIAID).
Giuseppe Scala of NIAID described a very different
approach to developing new antigens, based on screening large
libraries of random peptides displayed on the surfaces of
bacterial viruses (bacteriophages). The strategy was to select
those phages recognized by antisera from HIV-infected people,
which presumably contain peptides that mimic the
conformation of an authentic HIV epitope. In this way the
researchers identified five "mimotopes" (antigenic mimics)
recognized by neutralizing antisera to HIV-subtype B; these
also bound to antisera against subtypes A, C, D, E and F As
antigens, the mimotopes induced epitope-specific neutralizing
antibodies in mice. Studies of their immunogenicity in
monkeys are now in progress.
Natural Resistance to SIV in Mamu-A*01 Monkeys
Genoveffa Franchini (NCI, Bethesda) presented a surprising
result from a study of SIV vaccines in a 70-monkey study:
animals carrying the Mamu-A*01 histocompatibility allele
[belonging to a family of genes that regulates immune
responses] appear to have some natural resistance to SIV. This
finding emerged from an experiment designed to test a
canarypox-SIV vaccine with and without monomeric gpl120
boost, where even unvaccinated Mamu-A*01 monkeys (but not
animals with other alleles) were able to control viremia after
challenge. They also had less CD4+ cell loss and a delayed
disease progression relative to macaques with other alleles.
This ability to control viral load is associated with the presence

of CD8+ T-cells that recognize gag, env and tat, especially in
lymphoid tissue associated with the gastro-intestinal tract. "If
canarypox vaccine studies had been done only in Mamu-A*01
animals, any reasonable researcher would conclude that the
vaccine had no activity at all," said Franchini. To avoid such
misleading results, she emphasized that experimental vaccines
should be tested in a group of animals that is heterogeneous
with respect to the histocompatibility alleles.
Although eliminating the Mamu-A*01 animals reduced
the trial's statistical power, Francini could still show that
although canarypox-SIV did not protect against infection (since
nearly all animals became infected after challenge), it did
decrease viral load, protect against CD4+ cell loss and increase
overall survival. In terms of CTL responses, 20% of the
vaccinated animals had CTLs against gag or env at all 3 times
measured; 50% were positive twice and 70% once. Animals
receiving the gpl20 boost developed neutralizing antibodies to
the homologous lab strain of SIV but not against heterologous
viruses.
Other HIV Vaccine Candidates in Animals
Although inactivation of whole viruses is a classical strategy
used to make many licensed vaccines, there has been
relatively little work (or optimism) on this approach for HIV.
One of the few efforts is that of Larry Arthur and collaborators
(Frederick Cancer Research Center, Maryland), who developed
a method for chemically inactivating HIV or SIV that
preserves the virions and their immunogenicity apparently
intact. Under development for several years, Arthur presented
results from a small study of whole killed SIV vaccines, which
showed that 5/6 macaques were protected against the
homologous strain of SIV, but that the vaccine did not protect
against heterologous strains. Since the heterologous strain
used in the latter experiments was low in surface gp 120 (a
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