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Novel Vaccine Candidate Trial Brings Science Closer to Developing a Fully Protective HIV Vaccine

On March 27, 2019, IAVI and partners launched the clinical trial of a new HIV vaccine candidate. The clinical trial named IAVI W001 is at the first step in testing the experimental vaccine in humans (Phase I) and will enroll 60 healthy adult volunteers in Seattle, Boston, and Nairobi.

antibodies attached to trimer
Electron microscopy reconstruction depicting antibodies attached to the HIV Envelope glycoprotein trimer at five sites of vulnerability shown in different colors. (Courtesy of Andrew Ward and Christina Corbaci at Scripps Research.)

Over the next two years, the IAVI W001 trial will test the vaccine candidate called BG505 SOSIP.664gp140. The trial will answer questions on how safe the vaccine is and how well it can induce the human body to produce antibodies that can neutralize HIV. These are called neutralizing antibodies (NAbs). BG505 SOSIP.664gp140 belongs to a new generation of immunogens (molecules that are capable of causing an immune response in the body) called native-like trimers.

HIV is covered by an envelope protein (Env), which is shaped like a three-pronged spike. This spike, known as a trimer, is a target for antibodies produced by the human immune system after infection. Some of these antibodies can block viral replication by preventing entry into cells. Native-like trimers are molecules that are designed to look like the spikes on the outer surface of HIV and can induce the body to develop neutralizing antibodies.

In late 1999, researchers observed that a Kenyan baby born HIV positive was able to produce antibodies that could neutralize multiple strains of HIV, similar to some adults that had lived with the infection over a long period of time. While the NAbs were not able to eliminate infection, the concept of producing such a response in non-infected individuals to provide protection against HIV infection was conceived. The design of the BG505 SOSIP.664gp140 immunogen is based on hypotheses on the best approaches to producing targeted immune responses.

For decades, scientists have collaborated in research to engineer the HIV Env protein in its native-like configuration. IAVI W001 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 proteins have tested the immunogenicity of only a portion of the Env structure or proteins that do not resemble the native structure. In animal testing, the BG505 SOSIP.664 gp140 vaccine candidate showed promising results by causing production of antibodies that neutralized an HIV-like virus. Investigators hope to see if a similar specific response is elicited in humans.

One of the goals of HIV vaccination is to produce a specific type of NAb known as a broadly neutralizing antibody (bNAb) capable of neutralizing a wide range of HIV strains. Scientists hope this study is one of the first steps in learning how to do this. It is hoped that this vaccine trial will allow researchers to better understand what is required to induce bNAb responses in humans and pave the way to developing a fully protective HIV vaccine.

(First published in IAVI Voices Newsletter – Issue 4, May 2019)