Scientists have taken the fight against HIV a step forward by demonstrating that cows can rapidly produce powerful antibodies after being immunised, a finding that holds out promise to the hunt for a vaccine against HIV. The study has been published in Nature.
The researchers injected HIV immunogens — proteins designed to mimic proteins on the surface of HIV— into the flanks of four calves and waited for their immune systems to respond. All four cows developed antibodies called bNAbs (broadly neutralising antibodies) to HIV in their blood as rapidly as 35 to 50 days following two injections, says a news release from the US National Institutes of Health (NIH), which supported the study.
Broadly neutralising antibodies are so named because they can neutralise multiple strains of a virus. While people who have contracted one strain of HIV develop antibodies that are often specific to that strain, bNAbs are much rarer. This has been an obstacle in the hunt for a vaccine against HIV.
About 10 to 20 per cent of people living with HIV naturally develop bNAbs to the virus, but usually only after about two years of infection. These bNAbs have been shown in the laboratory to stop most HIV strains from infecting human cells, and to protect animal models from infection. However, scientists have so far been unsuccessful in prompting the human immune system to produce bNAbs through immunisation. Further, NIH says in its release, questions remain about whether effective antibodies could be produced rapidly and at a scale suitable for widespread distribution.
Cattle may offer some help solving these problems, the researchers found. While cattle do not naturally acquire the human virus HIV, their immune systems have unique features that the researchers thought would allow them to produce potent antibodies when injected with HIV immunogens. While bovine bNAbs are not likely suitable for clinical use in humans in their current form, exploring this rapid production may help answer important research questions, NIH says.
“From the early days of the epidemic, we have recognised that HIV is very good at evading immunity, so exceptional immune systems that naturally produce broadly neutralising antibodies to HIV are of great interest — whether they belong to humans or cattle,” the release quotes Anthony S Fauci, director of National Institute of Allergy and Infectious Diseases (NIAID, part of NIH).
The researchers were supported by NIAID at the Scripps Research Institute, the International AIDS Vaccine Initiative and Texas A&M University. The Scripps Research Institute investigators isolated specific antibodies from the immunised calves to study their properties. One of these antibodies is particularly potent, NIH says. Called NC-Cow 1, it neutralised about two-thirds of a panel of diverse HIV isolates.
“A minority of people living with HIV produce bNAbs, but only after a significant period of infection, at which point virus in their body has already evolved to resist these defences,” NIH quotes Dennis R Burton, a lead author of the study, director of the NIH’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and scientific director of the IAVI Neutralizing Antibody Consortium at the Scripps Reserach Institute. “The potent responses in this study are remarkable because cattle seem to produce bNAbs in a relatively short amount of time. Unlike human antibodies, cattle antibodies are more likely to bear unique features and gain an edge over complicated HIV immunogens.”
While no one knows definitively why these powerful antibodies evolved in cattle, one theory holds that the key could be in long loops of bNAbs, called HCDR3, which are tied to the animals’ extensive gastrointestinal systems. The researchers note that a promising approach to HIV vaccine development may be to promote the human immune system’s development of long HCDR3 loops.
“HIV is a human virus,” said Devin Sok, a study leader and Antibody Discovery and Development Director at IAVI, “but researchers can certainly learn from immune responses across the animal kingdom.”