IAVI Report Vol. 2, no. 2

AIDS Vaccine Conference Report continued from page 1
"convinced that we will have a safe and effective vaccine to prevent infection
or disease."
David Baltimore reviewed the mission of the NIH AIDS Vaccine Research
Committee, which provides advice to the NIH on opportunities, gaps and
future directions in HIV vaccine research (see interview, page 7). Among the key
scientific challenges to developing an effective vaccine, he noted, were
generating broadly reactive neutralizing antibodies and cytotoxic T-lymphocytes
(CTLs), developing methods to accurately measure cellular responses,
identifying optimum animal models and further understanding the determinants
of immune protection. Creating mechanisms to direct antigen presentation and
increase the immunogenicity of candidate vaccines,
particularly envelope components, he suggested, are

Recombinant Subunit Proteins
Uttle new data was presented to support or refute the popular hypothesis
that oligomeric forms of envelope proteins are more likely to provide
protection. Tom Van Cott of the Walter Reed Army Hospital reported that
an oligomeric form of gp 160, but not monomeric gp 120, protected three of
fifteen macaques from challenge with a nonpathogenic SHIV-HXB2. In
addition, when two of the protected macaques were boosted with an
oligomeric gp 120 and then rechallenged with heterologous nonpathogenic
SHIV, both remained protected. David Montefiori of Duke University also
presented a study showing that a number of different subunit protein

also critical areas of research.
Canarypox "Prime Boost"
Studies
A "prime boost" regimen, using a canarypox virus
vector prime ("ALVAC") and a gp 120 envelope protein
boost, has generated "good CTL responses and strong
neutralizing antibody responses against HIV lab
isolates," according to Pat Fast of NIAID. Results from
Phase I studies of ALVAC vCP205, produced by Pasteur
Mrieux Connaught, and a combination of an earlier
canarypox construct, vCP125, plus a gp120 boost,
produced by Chiron Corp., suggest that the vaccines
are safe and immunogenic. A Phase II trial of vCP205
plus a gpl20 boost has just begun. The trial will enroll
420 volunteers.
More details about the CTL responses generated by
the canarypox vaccines were provided by Kent
Weinhold of Duke University. Weinhold reported that
the vCP205 vaccine stimulated CTL activity in 50
percent of those given the vaccine. In comparison, only

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demonstrated that
an array of efforts
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immune system might
protect against HJT(
Howeverfew promising,
novel designs are
moving into Phase I
clinical studies.

vaccines were able to protect macaques against
challenge with a non-pathogenic SHIV. In addition,
protection correlated with levels of neutralizing
antibodies against the challenge virus. However
neutralizing antibodies induced by the vaccines,
including an oligomeric IIIBgp 140, failed to neutralize
primary isolates.
Marc Girard of the Pasteur Institute reported that
macaques immunized with either HIV envelope
(MN/LAI) or V3 lipopeptides were not protected from
challenge with pathogenic SHIV (89.6P) despite the
presence of strong neutralizing antibodies to HIV (MN).
DNA Vaccines
A number of studies were presented on the
immunogenicity of different DNA vaccine constructs.
New data suggests that these vaccines can elicit potent
CTL response and that these CTL responses can be
enhanced. However, many DNA vaccines still appear to
be weak in producing broadly neutralizing antibody and
no new data was presented showing either animal
protection or CTL killing of cells infected with
heterologous virus.

2 percent of individuals receiving gp 120 envelope vaccines developed a
measurable CTL response. He did note, however, that only 12 percent of
those given the canarypox vaccine maintained this CTL activity one year
after the last immunization. On a more optimistic note, Weinhold reported
that the canarypox constructs were able to generate CTLs in volunteers that
could neutralize cells infected with many different HIV subtypes found in the
world (see box). In addition, it was suggested that the techniques used to
expand and measure CTLs in vaccine recipients may not be detecting all
CTLs that are generated.
Pre-clinical "Prime Boost" Studies
A prime boost regimen, using a vaccinia vector (expressing HIV env) plus a
gp 120 boost can protect monkeys against challenge with non-pathogenic SHIV,
according to Shiu-lok Hu of the University of Washington at Seattle. The
combination protected all six monkeys from challenge with non-pathogenic
SHIV. On the other hand, Gunnel Biberfeld of the Karolinska Institute in
Stockholm presented data showing little protection against an intrarectal SIV
challenge in macaques injected with vaccinia (MVA) expressing a number of
SIV genes, plus SIV protein boosts. However, all four. macaques inoculated
twice with the MVA appear to have lessened disease progression. Studies
were also presented on a number of other vaccine vectors, including
adenovirus, rhinovirus, BCG and salmonella.

DNA vaccination of pregnant chimpanzees can induce significant anti-HIV
immune responses in newborns, according to data presented by Mark
Bagarazzi of the University of Pennsylvania. Bagarazzi reported that pregnant
chimps given HIV-DNA vaccine constructs produced antibodies to HIV,
transferred significant levels of these antibodies to their healthy newborns
and produced antibody (anti-env IgA) in their milk. Measurable HIV-specific
CTL responses were also seen in the newborns.
Jong Kim, also of the University of Pennsylvania, presented a study showing
that DNA vaccines that express co-stimulatory molecules could significantly
increase HIV-specific cellular responses. Related posters from this research
team, which is working with Apollon, Inc, a U.S.-based biotechnology company,
included data on a DNA vaccine containing a number of HIV genes that is
currently in animal studies. (Human studies of this vaccine should begin at four
U.S. sites by August, 1997.) Data was also reported on a Phase I trial of a
therapeutic DNA vaccine being tested for safety and immunogenicity in HIVinfected individuals.
A presentation by Margaret Liu of Merck & Co. provided additional information
about the company's ongoing HIV-DNA vaccine program. Liu reported that
multiple immunization of macaques with an HIV-DNA vaccine (encoding env) and
a gp 160 recombinant envelope boost, generated anti-envelope CTL responses
and protected against challenge with a non-pathogenic SHIV.
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