Scientists supported by the National Institutes of Health have achieved a significant step forward, eliciting broadly neutralizing antibodies (bNAbs) to HIV by immunizing calves. The findings offer insights for HIV vaccine design, and support further study of modified bovine antibodies as HIV therapeutics or prevention tools in humans, scientists reported in a paper published online in the journal Nature.

Researchers have observed that about 10 to 20 percent 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 immunization. Further, while bNAbs isolated from people with HIV infection have demonstrated promise in primate studies and have entered human studies for HIV prevention and treatment, 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, report researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, at the Scripps Research Institute (TSRI), the International AIDS Vaccine Initiative (IAVI) and Texas A&M University. 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, or proteins designed to mimic proteins on the surface of HIV.

In their study, the researchers injected HIV immunogens into the flanks of four calves and waited for their immune systems to respond. All four cows developed bNAbs to HIV in their blood as rapidly as 35 to 50 days following two injections. This immunogen – a BG505 SOSIP trimer – can elicit HIV bNAb responses consistently and rapidly.

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.

"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 defenses," said Dennis R. Burton, PhD, a lead author on 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 TSRI. "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."