An experimental HIV vaccine was found to stimulate broad neutralizing antibodies in a small group of volunteers in a Phase 1 study. The findings show that the vaccine regimen, given twice at an interval of eight weeks, elicits an immune response against the human immunodeficiency virus.
The results of the clinical trial published on World AIDS Day Thursday Science magazineEstablishing “clinical proof of concept” to help stimulate immune responses against HIV infection, for which there is no cure and which causes the immune deficiency syndrome known as AIDS.
The vaccine, called eOD-GT8 60mer, has a “reliable safety profile” and resulted in 97% or 36 recipients of total antibody-stimulating antibodies, according to Scripps Research researchers Fred Hutchinson Cancer Center in the United States and the National Institutes of Health in Sweden and other institutions.
Antibodies are proteins made by the body’s immune system that help fight infections, and Broadly protecting antibodies They are known to eliminate many genetic variants of HIV, but have been difficult to target with a vaccine.
“Learning how to induce broad neutralizing antibodies against pathogens such as HIV, influenza, hepatitis C virus, or the betacorvavirus family presents a major challenge for rational vaccine design,” the researchers wrote. “Germline-targeted vaccine design offers one strategy to address this challenge.
EOD-GT8 is a 60mer vaccine candidate. Germ-targetingIt is designed to induce the production of broad-spectrum neutralizing antibodies by targeting and stimulating specific antibody-producing cells.
Global AIDS vaccine initiative announced The beginning of this phase 1 clinical trial In the year 2018 to evaluate the safety and immune responses of eOD-GT8 60mer.
The trial enrolled a total of 48 healthy adults, ages 18 to 50, at the George Washington University in Washington and the Fred Hutchinson Cancer Center in Seattle.
Eighteen of the participants received a 20-microgram dose of the vaccine and eight weeks later the same dose of vaccine with an adjuvant; 18 100-microgram dose of vaccine and after eight weeks, the same dose of vaccine with adjuvant; and 12 received a saline placebo twice eight weeks apart. The adjuvant is called AS01B, developed by the pharmaceutical company GSK. The vaccines and placebo were given into the arm muscle.
The researchers collected and analyzed immune cells from the participants’ blood and lymph nodes during the study. They specifically looked at how B cells, a type of white blood cell that produces antibodies in the immune system, responded to the vaccine.
The researchers did not find any serious adverse events reported among the study participants, and no participants acquired HIV infection during the study. Of the 48 study participants, 97 percent—or all but one—reported generally mild or moderate local or systemic adverse events, such as injection site pain, soreness, and headache. In most cases, these incidents are resolved within a day or two.
After the first vaccination, all vaccine recipients but no placebo recipients were found to develop antibodies to the eOD-GT8 60mer vaccine. Those vaccine-induced reactions increased after the second vaccination, the researchers wrote.
Another Phase 1 study of this vaccine candidate is underway, said study author Dr. Julie McElrath, senior vice president and director of the Division of Vaccines and Infectious Diseases at the Fred Hutchinson Cancer Center.
This HIV vaccine candidate is unique in that it is designed to directly target the production of broadly neutralizing antibodies, said Dr. Timothy Shaker, associate dean and program director for HIV treatment research at the Medical School of Minnesota. Involved in research.
“In HIV, when we’ve designed and tested vaccines in the past, they’ve never induced these broadly neutralizing antibodies,” he said. “Call them super antibodies if you will. Broadly neutralizing antibodies work more effectively. They are better at controlling things,” he said.
By showing that a broad range of antibodies can be induced by a vaccine, this new research could help inform the development of not only HIV vaccines, but other types of vaccines, Shaker said.
“The hope is that if you can create that kind of immunity in people, you can protect against some viruses, so we’ve had a lot of trouble designing effective vaccines,” he said. “So this is an important step.”
Although this is “exciting science,” much work needs to be done before this vaccine is available for public use, said Dr. Carlos Del Rio, associate director and executive dean of the Center for AIDS Research at Emory University. At Grady Health System for Emory School of Medicine, which was not involved in the new study.
“We know that broadly neutralizing antibodies are an effective strategy to prevent HIV,” Del Rio said. “We’re a long way from using this as a vaccine, but it’s really exciting science. … Investing in this kind of research is not just about developing a vaccine for HIV, but if this strategy works, it can be used for other vaccines.”
An HIV vaccine would likely need to generate these broadly neutralizing antibodies, or bnAbs, “antibodies that can recognize a wide variety of HIV strains and prevent HIV infection.” However, induction of bnAbs by immunization has so far proved impossible. “The main challenge is that bnAbs are rarely developed even during infection,” said Penny Moore of the University of the Witwatersrand and South Africa’s National Institute of Infectious Diseases. He wrote in an editorial It was published alongside the new study.
A “key question” that still needs to be answered is how long the antibodies from the first vaccine can last.
Also, if the booster vaccine is very different from the previous vaccine, “antibodies induced by the first vaccine may not recognize the booster and will not mature further,” Moore wrote. “However, the inclusion of many different vaccines into the HIV vaccine regimen is unpalatable. Getting the balance right between antibody maturation to bnAbs and potential in the real world is critical.
Last year, more than 38 million people worldwide were living with HIV or AIDS. More than 20 HIV vaccine clinical trials are underway worldwide. According to the global AIDS vaccine initiative.
Many people in the United States have switched to daily HIV prevention pills or frequent injections. It is known as PREPTo reduce the risk of infection.
“It’s either a daily pill or a painful shot. It’s an awkward shot at most that you have to get several times a year,” Shaker said of PREP.
But he said the availability of an HIV vaccine would make the virus more accessible. “If you can vaccinate, you’ll reach more people, and if you have an effective vaccine, you’ll provide more and better coverage to reduce the chance of transmission if you’re exposed.”