An experimental vaccine designed to prevent HIV (human immunodeficiency virus) has produced promising results in a preliminary study involving a small group of volunteers.
The vaccine candidate showed success in stimulating production of rare immune cells needed to start the process of generating antibodies against the fast-mutating virus.
As detailed December 2 in the journal Science, the treatment produced a broad neutralizing antibody response in 35 of 36 (97 percent) of recipients who received two vaccine doses eight weeks apart.
“With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties, and this targeted stimulation can be very efficient in humans,” said William Schief, PhD, a study author and immunologist at Scripps Research, in La Jolla, California, in a press release.
“We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens,” added Dr. Schief, who is also the executive director of vaccine design at the IAVI Neutralizing Antibody Center, which developed the vaccine candidate (called eOD-GT8 60mer).
Schief and his colleagues stress that a preventive HIV vaccine is urgently needed to put an end to the HIV/AIDS epidemic, which began in the early 1980s. Although HIV infections have declined since then because of effective HIV prevention strategies, the World Health Organization (WHO) estimates that 38.4 million people globally were living with HIV by the end of 2021. More than 40 million have died of the virus, which causes AIDS (acquired immunodeficiency syndrome).
Currently, about 1.2 million people in the United States have HIV, and about 13 percent of them don’t know it and need testing, according to HIV.gov. HIV continues to have a disproportionate impact on certain populations, particularly racial and ethnic minorities and gay, bisexual, and other men who have sex with men (MSM).
“The current situation is difficult to sustain,” said Robert Shafer, MD, a professor of medicine at Stanford University in California who specializes in the treatment of infectious diseases.
“If new infections continue at this rate, the pandemic will not be contained,” added Dr. Shafer, underscoring the importance of developing an effective vaccine.
In this current trial, scientists have developed a unique vaccine regimen (referred to as “germ-line targeting”) that, in essence, primes the immune system by inducing rare but powerful antibodies that can neutralize diverse strains of HIV. Known as “broadly neutralizing antibodies,” or bnAbs, these specialized blood proteins could attach to HIV spikes, or proteins on the virus particle surface, that allow the virus to enter human cells, and disable them via important yet difficult-to-access regions that don’t vary much from strain to strain.
Shafer, who is not involved in the study, explained that HIV’s surface protein — called the “envelope” — is shielded by sugar molecules in most places. “There are only a small number of locations on the envelope that can be successfully targeted by neutralizing antibodies that can bind to the envelope and prevent HIV from getting into cells,” he said. “These bnAbs are able to snake their way into the few parts of the envelope that are not shielded by sugar molecules.”
In an editorial response published in Science, Penny Moore, PhD, with the University of the Witwatersrand and the National Institute for Communicable Diseases in South Africa, wrote that a key challenge has been that bnAbs rarely develop, even during infection. “Until now it has not been possible to elicit bnAbs by vaccination,” she wrote.
The vaccine candidate was able to stimulate the B cells, a type of white blood cell that produces antibodies that are precursors to one of the well-known types of bnAb, according to Shafer. “After the first immunization, approximately 1 in 10,000 circulating antibodies was a bnAb precursor,” he said. “After the second immunization at week 8, approximately 1 in 1,000 circulating antibodies was a bnAb precursor.”
The vaccine also had a “favorable safety profile,” creating no significant adverse events.
Further studies involving a larger group of participants is required to prove the effectiveness of the vaccine, says William Schaffner, MD, an infectious-disease specialist and professor of preventive medicine and health policy at the Vanderbilt University School of Medicine in Nashville, Tennessee.
“All they’ve done so far is draw blood and then go to the laboratory to measure the antibodies produced,” says Dr. Schaffner, who was not on the research team. “There have been previous vaccines of various types that look promising in the laboratory but once it got into humans, they weren’t very effective. So the proof will be in the pudding, so to speak. You have to see whether it actually prevents disease, because after all, that’s why the vaccine is being developed.”
The researchers noted that the current study uses a protein-based vaccine model, but they are also working with Moderna to develop an mRNA-based model similar to the platform used for Moderna’s COVID-19 vaccine.
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