IAVI Report Vo. 5, no. 2

ORAL HIV VACCINE
continued from page 1

delivered by the Salmonella was developed by Oxford
University's Andrew McMichael as part of IAVI's first
partnership. (See IAVI Report, January-March 1999.)
Unlike most viral vectors, bacteria can hold large amounts of
foreign DNA, are highly stable, and are simple and inexpensive
to manufacture. This bacterium also offers the potential to
deliver vaccines orally or intranasally. Because it is orally
administered, the new vaccine is expected to elicit mucosal
immune responses, which are thought to be the first line of
defense against sexually transmitted HIV.
"This vaccine approach stresses ease of use and low cost,
which are key factors for reaching people in developing
countries," said Seth Berkley, president of IAVI. Berkley also
noted that, like IAVI's three previous VDPs, the new agreement
includes legal guarantees to help ensure that any successful
vaccine will be distributed in developing countries for a
reasonable price. The simple manufacturing process, he added,
could also eventually allow this vaccine to be produced in
developing countries.
Gallo, the co-discoverer of HIV, noted that "this new
bacterial vector induces responses not only to microbes but to
certain cancers as well. IAVI's fast-track philosophy and
technical assistance will help speed this approach into human
tests."
Uganda was the first country in Africa to host an AIDS
vaccine trial. According to Francis Omaswa, the country's
director-general of health services, "Our new partnership with
IAVI will help ensure that we maintain our leadership in this
area, doing whatever we can to accelerate the development
and testing of AIDS vaccines appropriate for use in Africa."
The Salmonella-DNA vaccine, says Wayne Koff, IAVI's vice
president for research and development, "links two
independent vaccine strategies (orally administered
recombinant Salmonella vectors and DNA vaccines) with the
goal of improving upon both."
Koff noted that using the HIV DNA vaccine developed by
the Oxford-Nairobi partnership "will enable us to move this
new product into clinical trials faster, and compare it directly
with the Oxford group's injectable DNA vaccine. Head-to-head
comparisons of candidate vaccines in Phase I trials is an

integral component of our overall program."
The new Salmonella-DNA vaccine approach is the result of
intensive basic research on the delivery of HIV vaccines by
bacterial vectors, carried out by George Lewis, director of the
IHV Division of Vaccine Research, and fellow researcher David
Hone.
The DNA vaccine encodes pieces of HIV gag and
polyepitopes. According to Lewis, studies in mice show that a
Salmonella vector carrying foreign DNA generated significantly
greater CTL responses than the same vector expressing the
foreign proteins.
The Salmonella vector developed by the IHV researchers has
already been tested in 37 people in a Phase I trial funded by
the U.S. National Institute of Allergy and Infectious Diseases
(NIAID). That vector, which is engineered to express HIV
envelope proteins, has reportedly shown limited immune
responses. Researchers are now evaluating whether higher
doses of the vector will generate better responses. NIAID is
also supporting development of Salmonella to deliver DNA
which encodes a novel envelope antigen.
The disappointing immune responses seen with the lower
doses could be the result of "over-attenuating" the vector,
making it so weak that it is no longer immunogenic enough.
IHV researchers say they are waiting for results from the higher
doses before making any final conclusions about the vector's
immunogenecity. They also note that because the trial was the
first-ever human study of an HIV bacterial vector, they had to
make sure it was safe and did not induce Salmonella disease
(i.e., diarrhea) in participants.
If that strain of Salmonella is determined to be sufficiently
immunogenic, human trials of the Salmonella-DNA vector could
begin within 18 months, according to Lewis. The research
team is also looking at a range of other attenuated Salmonella
strains that could be used.
Anthony Fauci, director of NIAID, told a reporter that the
vaccine is "theoretically the right approach." However, he
cautioned that "we've been fooled so many times about new
vaccines that I've hesitated to talk about this one until now, but
I really like it." *

U.S. VACCINE BILL
continued from page 11

her HIV/AIDS initiative. She did not have to wait long for
President Clinton to act: he signed an Executive Order on 10
May that for the first time allows developing countries to
import and manufacture cheaper version's of the world's most
effective AIDS drugs without fear of punishment from U.S.
trade authorities. The following day the Senate, too, easily
passed the trade bill.
European Proposals Being Considered
The European Commission is also examining the possibility of
using tax credits to spur private sector investment in AIDS

vaccines. But observers believe that such credits are more
likely to be part of a broader plan designed to stimulate vaccine
development, which will be proposed by the European Commission to Parliament and Council in the coming months. In
terms of tax credits for vaccine development, one key question
still needing clarification is whether such programs can be
instituted, given European investment and competition. *
Allison Bauer is the policy director of the Washington, DCbased AIDS Vaccine Advocacy Coalition.

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