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IAVI Announces First-in-Human Clinical Trial of Native-like HIV Envelope Vaccine Candidate

Phase I Trial to Evaluate Safety and Immunogenicity of Engineered
Envelope Protein

NEW YORK–(BUSINESS WIRE)–The International AIDS Vaccine Initiative (IAVI) announced the start of
a Phase I clinical trial (IAVI W001) to test a novel HIV vaccine
candidate, BG505 SOSIP.664 gp140. The aim of the trial is to assess the
safety of the candidate and to determine if vaccination induces the
human immune system to produce proteins known as neutralizing antibodies
(NAbs).

Mark Feinberg, M.D., Ph.D., president and CEO of IAVI, said, “This trial
is unique because it represents the fruition of decades of scientific
research to engineer this promising vaccine candidate. Much important
work was done in the late 1990s and early 2000s to attempt to stabilize
the HIV envelope protein in its native configuration, but this difficult
work took several more years to achieve.”

BG505 SOSIP.664 gp140 is based on the HIV envelope protein (Env), which
is shaped like a three-pronged spike. This configuration, known as a
trimer, is a target for antibodies produced by the human immune system
after infection. Some of these antibodies are able to block viral entry
into cells.

The BG505 SOSIP.664 gp140 trimer was engineered by a team directed by
John P. Moore, Ph.D., at the Weill Cornell Medical College; Rogier
Sanders, Ph.D., now at the University of Amsterdam Academic Medical
Center; and Andrew B. Ward, Ph.D., and Ian A. Wilson, D.Phil., at
Scripps Research. The outcome of their work was an important advance in
stabilizing the highly fragile Env protein in a native-like
configuration.

This is one of the first clinical trials of a native-like Env trimer,
and the first time that this particular trimer is being evaluated in
humans. Previous vaccine trials involving Env concepts have tested the
immunogenicity of only a portion of the Env structure or proteins that
do not resemble the native structure. In animal testing, vaccination
with BG505 SOSIP.664 gp140 caused B cells to produce antibodies that
neutralized the virus type from which the engineered immunogen was
derived. Investigators hope to see a similar specific response in humans.

Many vaccine researchers agree that a goal of HIV vaccination will be to
produce a particular type of NAb known as a broadly neutralizing
antibody (bNAb). These antibodies can neutralize a wide range of
genetically variable HIV strains in laboratory tests, and studies show
that some bNAbs can protect monkeys against a virus that is similar to
HIV. This suggests that a vaccine that is able to induce similar
antibodies in people might protect them against HIV infection.

Though it is not likely that vaccination with BG505 SOSIP.664 gp140 on
its own will directly lead to the production of bNAbs, the hope is that
it could allow researchers to better understand what is required to
induce bNAb responses. As Bruce D. Walker, M.D., trial collaborator at
the W001 Boston trial site and director of the Ragon Institute of
Massachusetts General Hospital, MIT, and Harvard, notes, “This is a
critical trial that has broad implications for defining the path to
generating broadly neutralizing antibodies that will be needed for a
fully protective vaccine.” Data from the trial will likely contribute to
the development of the vaccine candidate for future trials.

Collaborators in the trial include the Fred Hutchinson Cancer Research
Center, Seattle HIV Vaccine Trials Unit; Kenya AIDS Vaccine
Initiative–Institute of Clinical Research, University of Nairobi, Kenya
(KAVI-ICR, Nairobi); Massachusetts General Hospital, Translational and
Clinical Research Center (Boston); and the pharmaceutical company GSK.
Julie McElrath, M.D., Ph.D., senior vice president and director of the
Vaccine and Infectious Disease Division, is the principal investigator
at Fred Hutchinson Cancer Research Center. Dr. McElrath said, “We hope
that presenting this trimer to the human immune system will give us a
unique view into a process that we want to harness to design an
effective HIV vaccine.”

Professor Omu Anzala, MBChB, Ph.D., of the University of Nairobi and the
Kenya AIDS Vaccine Initiative, and principal investigator at the
KAVI-ICR site, said, “Every HIV vaccine trial generates new information
that brings the international community closer to the discovery of a
safe, effective HIV vaccine. We and our partners are excited about the
new candidate and this new approach as we begin this trial.”

Dr. Feinberg added, “We are gratified and invigorated by the cooperative
spirit that binds the different institutions and researchers that have
developed the candidate and are conducting the trial. This collaborative
effort gives us great encouragement that the scientific community will
succeed at developing an effective HIV vaccine.”

The IAVI W001 trial will enroll approximately 60 healthy adult
volunteers in Seattle, Boston, and Nairobi. Participants will receive
three administrations of BG505 SOSIP.664 gp140 formulated with the AS01B1
adjuvant developed by GSK, or placebo. Adjuvants are substances used to
enhance immune responses induced by a vaccine, and the AS01 adjuvant is
used in licensed vaccines. The vaccine candidate is administered through
intramuscular injection. Teams at the trial locations will monitor
participants to assess the vaccine candidate’s safety and ability to
elicit immune system responses.

Results of the IAVI W001 trial are expected in 2020.

Research supported by the National Institutes of Health (NIH)/National
Institute of Allergy and Infectious Diseases (NIAID) through an HIV
Vaccine Research and Design (HIVRAD) grant and by IAVI contributed to
the development of BG505 SOSIP.664 gp140.

Development and manufacturing of clinical trial material were supported
by a Collaboration for AIDS Vaccine Discovery (CAVD) grant from the Bill
& Melinda Gates Foundation to IAVI’s Neutralizing Antibody Center (NAC),
an NIH/NIAID grant to the Scripps Center for HIV/AIDS Vaccine Immunology
and Immunogen Discovery (CHAVI-ID), and an NIH/NIAID HIVRAD grant to the
Weill Cornell Medical College. HIV clinical research activities
conducted at Kenya AIDS Vaccine Initiative, as well as a range of
important components of the research performed at the NAC, are made
possible by the generous support of the American people through the
United States Agency for International Development (USAID).

The IAVI W001 clinical trial is sponsored by IAVI and funded by USAID
and the Dutch government through the Dutch Ministry of Foreign Trade &
Development Cooperation. Additional funding is provided by the Fred
Hutchinson Cancer Research Center, Seattle HIV Vaccine Trials Unit; the
Ragon Institute; and the Bill & Melinda Gates Foundation.

About IAVI

The International AIDS Vaccine Initiative (IAVI)
is a nonprofit scientific research organization dedicated to addressing
urgent, unmet global health challenges including HIV and tuberculosis.
Our mission is to translate scientific discoveries into affordable,
accessible public health solutions for the people who need them most.

IAVI’s work is made possible by generous support from many donors
including: the Bill & Melinda Gates Foundation, the Coalition for
Epidemic Preparedness Innovations, the Ministry of Foreign Affairs of
Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with
The World Bank, the Ministry of Foreign Affairs of the Netherlands, the
United Kingdom Department for International Development, and the United
States Agency for International Development (USAID). USAID administers
the U.S. foreign assistance program providing economic and humanitarian
assistance in more than 120 countries worldwide. The contents are the
responsibility of the International AIDS Vaccine Initiative and do not
necessarily reflect the views of USAID or the United States government.
The full list of IAVI donors is available at www.iavi.org.

1 The GSK proprietary AS01 adjuvant system contains QS-21
Stimulon® adjuvant licensed from Antigenics LLC, a wholly owned
subsidiary of Agenus Inc. (NASDAQ: AGEN), MPL and liposomes.

Contacts

Media
Rose Catlos
[email protected]
+1-212-847-1049

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