In a Phase 1 study, a new HIV vaccine was found to produce broadly neutralizing antibodies in a small number of volunteers. These results suggest that two doses of the vaccine can produce immune responses against the human immunodeficiency viruses, given eight weeks apart.
Published Thursday, World AIDS Day, in Science, the clinical trial results provide “clinical proof” that boosting regimens can be used to induce immune responses against HIV infection. There is no cure for HIV, which can lead to acquired immunodeficiency syndrome (AIDS).
According to researchers from Scripps Research and the Fred Hutchinson Cancer Center as well as the National Institutes of Health, the vaccine, EOD-GT8-60mer, had a favorable safety profile and induced broadly neutralizing antibodies in 97% of the 36 recipients.
Antibodies are proteins that the immune system makes to fight infections. Although broadly neutralizing antibodies can neutralize many variants of HIV genetically, they are difficult to induce by vaccination.
Researchers wrote that “Learning how to induce broadly neutralizing antibodies against pathogens of high antigenic diversity such as HIV, influenza or the family betacoronaviruses represents a great challenge for rational vaccine design.” This challenge can be met by a germline-targeting vaccine design.
The eODGT8-60mer vaccine candidate was germline-targeting. This means it is designed to stimulate the right antibody-producing cells and induce broadly neutralizing antibodies.
Inducing “super antibodies”
International AIDS Vaccine Initiative has announced that a Phase 1 clinical trial will be conducted in 2018 to assess the safety and immune response of EOD–GT8 60mer.
There were 48 healthy adults between the ages of 18 and 50 who participated in the trial. They were enrolled at Fred Hutchinson Cancer Center in Seattle and George Washington University in Washington.
18 participants received a 20 microgram dose of vaccine, followed by an eight-week-long dose with the same adjuvant. 18 also received a 100 microgram dose and eight weeks later a similar-sized dose with the adjuvant. Twelve received two doses with a saline placebo. GSK, a pharmaceutical company, has developed the adjuvant AS01B. The arm muscle was infected with the vaccines and placebo.
During the study, researchers collected immune cells from blood and lymph nodes and analyzed them. The researchers focused on how the vaccine affected B cells (a type of white blood cell that produces antibodies in the immune system).
Researchers found that no serious adverse events were reported by study participants. Also, no participant contracted HIV during the study. The majority of study participants, 97%, reported mild to moderate adverse reactions, including headaches, malaise, pain at the injection site, and malaise. These events are usually resolved in a matter of days or less.
All vaccine recipients, but none of the placebo recipients, produced antibodies after the second immunization. Researchers found that vaccine-induced immune responses were more prevalent after the second immunization.
A Phase 1 study of this vaccine candidate is ongoing, according to Dr. Julie McElrath (senior vice president and director, of the vaccine and infectious disease division, Fred Hutchinson Cancer Center), who was also an author of that study.
This HIV vaccine candidate is unique because it was engineered specifically to target the production of broadly neutralizing antibodies, according to Dr. Timothy Schacker, vice-dean for research at the University of Minnesota Medical School. Schacker was not involved with the research.
He said that HIV vaccines have not been shown to induce broadly neutralizing antibodies in any of the previous tests. These super antibodies can be called whatever you like. They work faster than the broadly neutralizing antibodies. They are more effective at controlling things.
Schacker stated that the new study has shown that vaccines can induce broadly neutralizing antibodies. This could be an important step in developing other types of vaccines.
He stated that the hope is that, if you can instill this type of immunity in people you can protect them against some of the viruses that we have had a hard time developing vaccines that work. This is a significant step forward.
This is an “exciting science”, but there are still many things to do before the vaccine can be used in the general population, according to Dr. Carlos del Rio. He was co-director of Emory University’s Center for AIDS Research and executive associate dean for Emory Medical School at Grady Health System.
Del Rio stated that “we know that broadly neutralizing antibodies are a potentially effective strategy to prevent HIV.” Although we are far from developing a vaccine for HIV, this exciting science is still being developed. This type of investment is critical in developing a vaccine against HIV. If it works, then other vaccines can also be developed.
A ‘key question’
These broadly neutralizing antibodies (or bnAbs) are required for an HIV vaccine to be effective. They “can recognize HIV strains from all over the world and prevent infection.” However, vaccination has not been able to trigger bnAbs. “BnAbs are rare, even after infection,” Penny Moore of the University of the Witwatersrand, and the National Institute for Communicable Diseases of South Africa wrote in an editorial that was published with the new study.
The “key question” is still to be answered about how long the antibodies elicited from the first vaccination can last.
Moore also noted that booster shots may be too different than the ones given before. “Antibodies that were triggered by the initial vaccination may not recognize the booster, and will not mature further.” However, it is not feasible to include multiple shots in an HIV vaccine regimen. It will be crucial to strike the right balance between antibody maturation towards bnAbs, and practicality in the real world.
More than 38 million people around the world were living with HIV/AIDS last year. According to the International AIDS Vaccine Initiative, more than 20 HIV vaccine clinical trials continue around the globe.
To reduce their chances of getting infected, many Americans have taken daily HIV-prevention pills and frequent injections (known as PrEP).
It’s either a daily pill or a painful shot. PrEP is a painful shot, which Schacker stated about it.
He said that having an HIV vaccine would make it easier to protect yourself against the virus. “If you can provide a vaccine, you will reach more people. If you have an effective vaccine you can also provide more coverage to lower the chance of you being exposed.