In a considerable win for HIV prevention science, researchers have succeeded in immunizing calves and prompting them to produce so-called broadly neutralizing antibodies for the virus. This success likely opens the door for considerable future scientific discovery in the effort to develop new, effective means of preventing the virus, including vaccines and pre-exposure prophylaxis (PrEP). Researchers are eager to continue further research of modified bovine antibodies for use in humans.
National Institutes of Health (NIH)–funded researchers published their findings of this calf-based study in the journal Nature and will also present their research on July 25 at the 9th International AIDS Society Conference on HIV Science in Paris (IAS 2017).
According to previous research, about 10 to 20 percent of people with HIV will naturally develop broadly neutralizing antibodies. These virus-fighting antibodies are highly effective at neutralizing a wide variety of strains of the virus. However, people who develop them typically do so a year or two into their infection, by which point these antibodies are unable to thwart that individual’s well-established infection. Thus far, scientists have not been able to prompt humans to develop broadly neutralizing antibodies through an immunization.
However, in animal research, broadly neutralizing antibodies have successfully prevented infection, raising the possibility that their power could be harnessed for HIV prevention among humans. Promising primate-based research in this area has already led to major human trials of infusions of the antibodies as PrEP.
Even if researchers do find a way to use broadly neutralizing antibodies, whether in vaccine form or as PrEP to prevent HIV among humans, a major question hangs over this field: Will producing a sufficient quantity of antibodies rapidly enough to satisfy widespread need be feasible?
The pharmaceutical industry commonly relies on animals such as cattle, chicken and pigs to produce large antibodies for human treatments, vaccines and even therapeutic hormones. So the HIV prevention effort may turn to this production model as well.
In the new calf-based HIV study, researchers injected immunogens (proteins designed to mimic proteins on HIV’s surface) into the flanks of four calves. All four young cows developed broadly neutralizing antibodies to HIV in their blood, as quickly as 35 to 50 days after the injections—an impressively swift immune response.
These particular antibodies are not likely suitable for use in humans in their current form. However, further investigation into the calves’ rapid production of antibodies could shed light on pressing HIV-prevention research questions.
After isolating specific antibodies from the calves, the researchers studied them closely. One particularly potent antibody, they found, binds to a key site on HIV’s surface that the virus uses to attach to infect immune cells. Quaintly named NC-Cow 1, the antibody neutralized about two thirds of a range of HIV isolates that the scientists tested it against. The antibody’s activity bore similarities to a human-derived broadly neutralizing antibody known as VRC01 that has shown promise in numerous studies and is the basis of the current antibody-based PrEP trials. VRC01 neutralizes 90 percent of HIV strains but is less potent than NC-Cow 1.
Going forward, scientists may pursue mimicking or modifying NC-Cow 1 or other antibodies like it for use in vaccine efforts or PrEP as well as for treatments for other pathogens that have evolved to evade the human immune system.
To read a press release about the study, click here.
To read the study abstract, click here.