It has been more than three decades since HIV was discovered and the virus, which causes Aids, has claimed more than 35 million lives.
Although effective antiretroviral drugs mean that people can live with HIV for decades, the optimal drug treatments to prevent resistance developing are not universally available. Last year alone, HIV-linked conditions claimed more than one million lives.
The continued death toll from HIV highlights the importance of developing improved ways to prevent infections, of which there were nearly two million last year, according to the World Health Organisation.
A vaccine that confers immunity to HIV has proved difficult to develop, despite considerable effort by researchers. The nature of HIV partly explains these difficulties – the virus exists in many different forms and evolves rapidly.
Efforts to prevent the spread of HIV continue, however, and have now turned to what might seem a surprising source: camels in the UAE.
The Central Veterinary Research Laboratory (CVRL) in Dubai has played an important role in research looking at whether antibodies produced by camels could be used to combat HIV. Recently published in the journal Scientific Reports, the work indicates camel antibodies have great potential. In tests, a combination of two particular types of antibody isolated from camel blood was able to neutralize most HIV strains from different subtypes tested.
“The approach we are following now is promising to protect from new infections in groups at high risk of sexual HIV transmission,” said Dr Ursula Dietrich, the scientist leading the project at the Georg Speyer Haus, a research institute in Frankfurt, Germany.
It was thought that camels might prove useful in the fight against HIV because part of the antibodies they produce are much smaller than those generated by most other animals, including humans. Known as “nanobodies”, these smaller structures are derived from antibodies consisting solely of two heavy chains of amino acids – the protein building blocks – while typically antibodies are made of two heavy chains and two light chains. They also have some features typically found in broadly neutralizing human antibodies, which are effective against multiple HIV strains.
Previous research had found that nanobodies show promise for combating a number of other illnesses affecting people.
Dr Dietrich’s laboratory provided the CVRL with “spike”-like proteins from the HIV “envelope”, which is located on the surface of the virus and responsible for its infectivity. These envelope proteins are exposed to the immune system and are the target of neutralizing antibodies. The proteins were derived from HIV subtype C, the virus’s most common form.
At the CVRL, these envelope proteins were injected once a week for six weeks into four camels to stimulate an anti-HIV immune response.
“The camel recognises it as a foreign body and wants to get rid of it and it produces antibodies,” said Dr Ulrich Wernery, the scientific director of the CVRL, who carried out the Dubai part of the research.
Dr Wernery took blood samples from the camels and these were analysed by the researchers, who were interested in the type of nanobodies that had been produced.
More than two dozen nanobodies were identified by Dr Dietrich’s group and tested in the laboratory against various “subtypes” of HIV.
When the actions of two nanobodies were added together, VHH-A6 and VHH-28, they were effective against 19 out of 21 strains of the most common and harmful type of HIV, known as HIV-1. The other main type of the virus, HIV-2, is largely restricted to West Africa and is less potent in its ability to cause illness.
“I was expecting a certain breadth, but yes, I was surprised that the combination of our best two nanobodies neutralized 19 out of 21 HIV-1 strains of our standard virus panel, which includes the major HIV-1 subtypes, in particular subtype C, which accounts for more than half of the infections worldwide,” said Dr Dietrich.
Among the other researchers involved in the project is Dr Eric Geertsma, a junior professor at the Institute of Biochemistry at Goethe University Frankfurt. He described nanobodies as having “massive potency”.
“There may be more need to optimise them and find better ways [to improve] this neutralisation capability, [but] it’s a promising start,” he said, adding that nanobodies were also helpful in allowing researchers to study membrane proteins.
When it comes to preventing HIV infection, Dr Dietrich is now leading an effort to use the nanobodies to confer “passive immunity” to individuals. Passive immunity describes a situation in which antibodies are directly supplied to a person. It contrasts with “active immunity”, which happens when that person’s body produces the antibodies itself when they have, for example, been immunised against a virus, usually by injecting them with components of that virus in a form that is incapable of producing illness.
In work being done in collaboration with researchers in Stockholm in Sweden and Cologne in Germany, Dr Dietrich and her co-researchers are genetically engineering probiotic bacteria to produce the camel nanobodies. The small size of the nanobodies makes it easier to genetically engineer bacteria to synthesise them. The aim is to achieve a high-level of expression of HIV neutralizing nanobodies in the vagina for passive immunization at the primary sites of sexual transmission of HIV-1.
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Given the difficulties in developing an HIV vaccine so far, however, Dr Dietrich is careful not to make predictions about how long it might take before the camel nanobodies can be used in a clinical setting to protect people from HIV.
She said: “When I started with HIV research in 1987, scientists said there would be an HIV vaccine in five to 10 years, meaning that since 20 years ago we should have had an HIV vaccine. Do we?”
She also said, however, that she was “very optimistic” that the approach she and her co-researchers are following could lead to effective preventative measures. If and when it does happen, nanobodies produced by camels at the CVRL in Dubai will have played a central role in the efforts, helping the global fight against HIV to take a potentially significant step forward.