IAVI Report Vo. 5, no. 2

Phase II "Prime-Boost" Trial to Begin in
Brazil, Haiti, and Trinidad
by Sam Avrett

A consortium of vaccine trial sites in Rio de Janeiro, Port-auPrince, and Port of Spain will begin enrolling volunteers in
June 2000 for a Phase II HIV vaccine trial. Planned since
March 1998, it will be the first international multi-site Phase II
trial of a preventive HIV vaccine, and only the fourth Phase II
preventive HIV vaccine trial ever conducted.
Funded by the U.S. National Institutes of Health (NIH), the
trial will enroll 120 people, 40 at each site. The research
protocol received final approval from nearly all governmental
and institutional review boards in late March (with a decision
from Trinidad and Tobago's AIDS Vaccine Ethics Committee
still pending as the IAVI Report went to press). All three sites
are now making final preparations for enrollment.
The trial will evaluate a "prime-boost" combination HIV
vaccine with two components: a canarypox vector (vCP1452,
manufactured by Paris-based Aventis Pasteur) carrying multiple
genes from an HIV subtype B strain, and an envelope protein
fragment (gp120MN, produced by VaxGen of San Francisco)
from a lab-adapted, B subtype-derived strain. Its main goal is to
generate more data on the safety and immunogenicity of the
canarypox vector, alone and in combination with the envelope
subunit vaccine. It will also raise the level of operational
experience in conducting an international multi-site trial,
including the collection of data and laboratory samples,
building laboratory capacity, and recruiting populations for
HIV vaccine trials, all of which may pave the way for future
HIV vaccine trials in these countries. (A Phase III trial of
canarypox plus gp120 is now under consideration by leaders of
the NIH-funded Vaccine Trials Network.)
According to research staff at the sites, the major challenge
in preparing for the trial was the political process rather than
the science. "There was a remarkably solid basis of
collaboration and support among the team of researchers from
Brazil, Haiti, Trinidad and Tobago, the U.S. NIH and Family
Health International," said Trinidadian researcher Farley
Cleghorn, "and this allowed planning to go very smoothly. Yet
the approval processes within our own country and in others
took a year to complete." Mauro Schechter, principal
investigator of the Rio de Janeiro site, described a similar
experience. "By and large, most people at the various Brazilian
agencies tried to be helpful, and because AIDS touches
everyone, most government officials understood the need for
this research," he said. "But, since this is the first international
multi-center trial, often officials were not able to tell us
precisely what approvals and documents were needed, and
from which ministry or agency. Now we know our way
through the maze."

Community groups in all three countries were involved
early in planning for the trial. "Our community advisory board
reviewed and commented on the protocol and informed
consent forms, and we will be glad to see this trial finally
enrolling," said Alexandre do Valle Menezes, head of the Rio
PWA group, Grupo Pela Vidda.
The trial will randomize 120 participants into three groups:
45 participants to receive three doses of the combination of
vCP1452 plus gp120MN (by intramuscular injection), 45 to
receive three doses of vCP1452 only, and 30 to receive
placebo. The trial volunteers will be mostly heterosexuals at
low risk for HIV, along with some homosexual men at the
Brazilian site. In addition to producing more immunogenicity
data on these vaccine products, the trial will collect data on
whether host factors such as HLA type, nutritional status or
concurrent infections affect the immune responses generated
by these vaccines.
The vCP1452 construct is the latest refinement in a series of
canarypox vectors developed by Aventis Pasteur. Containing
parts of HIV-1 genes env, gag, pol, and nef together with
vaccinia promoter sequences that boost gene expression,
vCP1452 has already been tested in approximately 50
volunteers and has shown no safety problems. Preliminary
data from a U.S.-based trial (AVEG 034) with 90 volunteers
indicate that vCP1452 elicits significantly higher levels and
frequencies of cellular immune responses than two other
canarypox products (vCP1433 and vCP205), although
vaccinees are still being followed so these results are not yet
final. In total, canarypox-based HIV vaccine candidates have
been tested for safety and immunogenicity in nearly 1,000
people in the U.S., France, and Uganda.
The subunit gp120MN envelope protein is a VaxGen
product that pre-dates their bivalent gp120B/B1qaz product
now in Phase III trials in the U.S., Thailand, and the
Netherlands. Derived from an early subtype B strain that was
adapted to grow in cultured cells, the gp120MN protein has
been tested for safety and immunogenicity in approximately
1,300 volunteers in the U.S. and Thailand.
The clinical trial sites for the current international Phase II
trial are the Hospital Escola Sao Francisco de Assis in Rio de
Janeiro, Brazil; the Institut National de Laboratoire et de
Recherches in Port-au-Prince, Haiti; and the Medical Research
Foundation in Port of Spain, Trinidad. *
Sam Avrett was the founding executive director of the AIDS
Vaccine Advocacy Coalition.