A new study has shown that a single injection of antibodies that target HIV can protect monkeys from contracting the virus for nearly six months. The study, published today in Nature, is an important step in the development of a new treatment that could prevent HIV infections in people. Because no HIV vaccine exists, finding other forms of preventive treatments against HIV is key.
In the study, American and German researchers used four powerful antibodies that are known for neutralizing several strains of HIV circulating around the world. The antibodies were produced by certain HIV-infected people and purified in a lab before being used in the study. The researchers injected four groups of macaques with a different antibody. A week after the monkeys were given the antibodies, they were exposed to weekly low doses of a monkey version of the HIV virus. (The human version only infects people.) The antibodies were found to protect the macaques from becoming infected for 12 to 14 weeks on average. Some animals were even protected for as long as 23 weeks. For monkeys without the antibody, it took an average of three weeks to become infected with HIV.
"I am astonished by how long protection lasted."
"The result is surprising," says Ruth Ruprecht, who directs the AIDS Research Program at Texas Biomedical Research Institute and did not take part in the study. "I am astonished by how long protection lasted."
Preventive HIV medications already exist, but they leave much to be desired. Pills like PrEP, for example, reduce the risk of getting infected from sex by more than 90 percent. The problem is that PrEP needs to be taken daily, and people often forget or they run out of pills or they take the medication only when they have sex. And that reduces the drug’s effectiveness. "PrEP is good if people take it, but we all know that human nature is such that we’re not perfect," says Ruprecht. "We forget things."
This is why scientists are looking for other medications that can prevent HIV infections. Creating a vaccine would be ideal, but that’s proven difficult. Antibodies could be an alternative to an HIV vaccine. A vaccine works by exposing a person to a weakened pathogen and basically teaching the person’s immune system to fight off the infection for several years. With the treatment tried in this study, people would be injected with the antibodies instead of producing them themselves. The question is how long people would be protected. The longer the protection, the better the treatment, because it’d require people to get injections less frequently. That’s key in parts of the world like Africa, where HIV is widespread but access to health care facilities much less so. Nearly 37 million people in the world live with HIV today; in 2014 alone, nearly 2 million people became newly infected.
Antibodies could be an alternative to an HIV vaccine
The study found that certain monkeys were protected for nearly six months with a single injection of antibodies. That’s promising, says David Montefiori, the director of the Laboratory for AIDS Vaccine Research and Development at Duke University, especially because the antibodies used in the macaques will be even more effective in people. In fact, monkeys create their own antibodies to fight off the human antibodies, causing the antibodies to stick around for a shorter period of time than they would in people. "What the data in this study is suggesting is that six months [of protection] may be achievable and with improved technologies we might even do better than that," says Montefiori, who did not take part in the study.
"This study is the first one to show that a single administration of these monoclonal antibodies can prevent infection, prevent disease, and might be a viable alternative for a vaccine against HIV," says Malcolm Martin, the director of the Viral Pathogenesis and Vaccine Section at the National Institute of Allergy and Infectious Diseases, who co-authored the study. "That’s a new finding."
The study is not completely groundbreaking: antibodies have already been used to delay HIV infection in macaques. But in most of those studies, the monkeys were infected with HIV with a single high-dose shot of the virus. In this study, the monkeys were instead exposed to the virus in low doses week by week, not all at once. That mimics the way that people get exposed to HIV in real life. In fact, people usually don’t get infected with HIV the first time they’re exposed to the virus, Ruprecht says. The infection happens gradually.
First, we have to see if the antibodies work in people
"People actually get exposed to a surprisingly low level of virus during individual unprotected acts of intercourse," says Ruprecht. "It’s surprisingly low the amount of infectious virus that gets passed from an HIV-positive person to a negative partner." For this reason, she says, the study "is a very good step in the right direction to reflect the biology of HIV virus among people."
The study has its limitations, at least for some. Ruprecht points out that the researchers could have achieved better results by using a cocktail of antibodies in the monkeys, instead of injecting each group of macaques with a single antibody. That’s because when an HIV virus is confronted by one antibody, the virus becomes resistant to it. "When you combine antibodies that have different specificities, you decrease the chance of creating immunization-resistant viruses," says Ruprecht. When mixed together, the antibodies "reinforce each other, synergize, and what that will mean is that the protection will be much more potent."
The study acknowledges that a cocktail of antibodies would be more efficient. But, Martin says, the researchers wanted to first figure out how effective each individual antibody was against the HIV virus. "Right now, we have to take things one step at a time," says Martin. "You can’t jump start in and automatically give a mixture of four antibodies." First, Martin says, we have to see if the antibodies work in people. Only then we can think of an effective cocktail treatment.
"Hopefully, we’ll see the light at the end of the tunnel within the next 10 years."
That’s what happening right now with one of the antibodies Martin used in his study. A clinical trial of the antibody VRC01 — the first one of its kind — has just begun in Brazil, Peru, and the United States. The study will enroll 2,700 people who are at high-risk of infection and it will test how effectively the antibody protects them from getting infected. Later this spring, the study will launch in several African nations, including South Africa, Kenya, Botswana, and Tanzania. If the results, which are expected by 2022, are good, antibodies could be developed into an effective preventive treatment, which would be profoundly important in the fight against HIV. Montefiori, who has devoted 30 years of his career to finding an HIV vaccine, says there are reasons to be positive.
"With the extraordinary progress that’s been made just in the past six years, I’m more optimistic than ever that the field will eventually succeed in having an effective prevention measure," he says, whether it’s the antibodies or an actual vaccine. "Hopefully, we’ll see the light at the end of the tunnel within the next 10 years."