HIV vaccine candidate elicits immune response in early clinical trial

CNN
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An experimental HIV vaccine was found to induce broadly neutralizing antibodies among a small group of volunteers in a first phase study. The findings suggest that a two-dose vaccine regimen, given eight weeks apart, can induce an immune response against human immunodeficiency virus.

The results of the clinical trial, published on Thursday on World AIDS Day in to the journal Scienceto establish a “clinical proof of concept” to support the development of a booster regimen to boost immune responses against HIV infection, for which there is no cure and which can cause acquired immunodeficiency syndrome, known as AIDS.

The vaccine, called eOD-GT8 60mer, had a “favorable safety profile” and induced broadly neutralizing antibodies in 97%, or all but one, of 36 recipients, according to researchers at Scripps Research, the Fred Hutchinson Cancer Center, the National Institutes of health and other institutions in the United States and Sweden.

Antibodies are proteins created by the immune system to help fight infections, and broadly neutralizing antibodies they are known to neutralize many genetic variants of HIV, but have been difficult to induce by vaccination.

“Learning how to induce broadly neutralizing antibodies against pathogens with high antigenic diversity, such as HIV, influenza, hepatitis C virus, or the betacoronavirus family, represents a major challenge for rational vaccine design,” the researchers wrote. “Germline-targeted vaccine design offers one potential strategy to address this challenge.”

The vaccine candidate is eOD-GT8 60mer germline-targetingmeaning it is designed to induce the production of broadly neutralizing antibodies by targeting and stimulating the right antibody-producing cells.

The International AIDS Vaccine Initiative has announced the start of this first phase of the clinical trial in 2018, to evaluate the safety of eOD-GT8 60mer and the immune responses it may induce.

The trial included a total of 48 healthy adults between the ages of 18 and 50, who were enrolled at two institutions: George Washington University in Washington and the Fred Hutchinson Cancer Center in Seattle.

Among the participants, 18 received the 20 microgram dose of vaccine and, eight weeks later, the same dose of adjuvanted vaccine; 18 received a 100 microgram dose of vaccine and, eight weeks later, an equal dose of adjuvanted vaccine; and 12 received two doses of saline placebo eight weeks apart. The adjuvant is called AS01B, and it was developed by the pharmaceutical company GSK. Vaccines and placebo were administered into the arm muscle.

The researchers collected and analyzed immune cells from the participants’ blood and lymph nodes during the study. In particular, they examined how B cells, a type of white blood cell that makes antibodies in the immune system, responded to the vaccine.

The researchers did not find any serious side effects among the study participants, and no participants acquired HIV infection during the study. About 97% — or all but one — of the 48 study participants reported local or systemic side effects that were generally mild or moderate, such as injection site pain, malaise and headache. In most cases, these events resolved within a day or two.

After the first immunization, all vaccine recipients but those receiving placebo were found to produce antibodies elicited by the 60-mer eOD-GT8 vaccine. These vaccine-induced responses increased after the second vaccination, the researchers wrote.

Another Phase 1 study of this vaccine candidate is underway, said Dr. Julie McElrath, senior vice president and director of the Division of Vaccines and Infectious Diseases at the Fred Hutchinson Cancer Center, who was an author of the study.

What is unique about this HIV vaccine candidate is that it is engineered to directly target the production of broadly neutralizing antibodies, said Dr. Timothy Schacker, associate dean for research and director of the HIV medicine program at the School of Medicine. faculty at the University of Minnesota, who were not involved in the research.

“With HIV, when we’ve designed and tested vaccines in the past, they didn’t induce these broadly neutralizing antibodies for whatever reason,” he said. “Call them super antibodies, if you like. Broadly neutralizing antibodies work more effectively. They are better at controlling things.”

By showing that broadly neutralizing antibodies can be induced by a vaccine, this new study could help develop other types of immunizations, not just HIV vaccines, Schacker said.

“We’re hoping that if you can induce this kind of immunity in people, you can protect them against some of these viruses that we’ve had a very difficult time developing vaccines for that are effective,” he said. “So this is an important step forward.”

While this is “exciting science,” much work needs to be done before this vaccine can be considered for public use, said Dr. Carlos del Rio, co-director of the Center for AIDS Research at Emory University and executive assistant dean for Emory School of Medicine at Grady Health System, which was not involved in the new study.

“We know that broadly neutralizing antibodies are a potentially effective strategy to prevent HIV,” del Rio said. “We are a long way from using this as a vaccine, but this is very exciting science. … Investing in this type of research is critical not only for HIV vaccine development, but if this strategy works, it can be used for other vaccines.”

An HIV vaccine will likely need to elicit these broadly neutralizing antibodies, or bnAbs, “which can recognize globally different strains of HIV and can prevent HIV infection. However, eliciting bnAbs by vaccination has so far proved impossible. A key challenge is that bnAbs rarely develop, even during infection,” Penny Moore of the University of the Witwatersrand and the National Institute of Infectious Diseases in South Africa, they wrote in the editorial published with the new study.

The “key question” that remains to be answered is how long the induced antibodies from the first immunization can last.

Also, if the booster is too different from the previous vaccine, “antibodies primed by the first vaccine may not recognize the booster and may not mature further,” Moore wrote. “However, incorporating many different injections into an HIV vaccine regimen is not attractive. Striking the right balance between the need to mature antibodies to bnAbs and real-world feasibility will be key.”

Last year, more than 38 million people were living with HIV or AIDS worldwide. More than 20 clinical trials of HIV vaccines are ongoing worldwide, according to the International AIDS Vaccine Initiative.

Many people in the United States have turned to daily HIV prevention pills or frequent injections, known as PrEPto reduce the risk of infection.

“It’s a daily pill or a painful injection. It’s an injection that’s uncomfortable at best and you have to get it a few times a year,” Schacker said of PrEP.

But the availability of an HIV vaccine would make protection against the virus more accessible, he said. “If you can give a vaccine, you’re going to reach more people and provide, if you have an effective vaccine, more and better coverage to reduce the likelihood of transmission if you’re exposed.”