Broadly neutralizing antibodies that can inhibit multiple strains of HIV can be generated rapidly in cows after repeated immunization with a protein that mimics the HIV envelope, reports a study published online in Nature this week. The findings may inform HIV vaccine design, although it remains uncertain whether the same approach could elicit a similar response in humans.
Broadly neutralizing antibodies are generated in a subset of people infected with HIV, and a goal of HIV immunotherapy is to produce a vaccine that could induce the generation of these antibodies. This effect has been difficult to achieve in in humans and a variety of animal models, possibly because some animals do not have sufficient precursors required to mature into broadly neutralizing antibodies. Cows, however, produce antibodies that may have greater potential to become broadly neutralizing. Thus, Dennis Burton and colleagues immunized four cows with a protein called BG505 SOSIP, which has been designed to mimic the HIV envelope - the outer membrane of the virus.
They observe rapid generation of broadly neutralizing antibodies following immunization; one cow produced antibodies capable of neutralizing 20% of the 117 HIV subtypes tested after 42 days, increasing to 96% breadth by 381 days. The length of time required to produce similar antibodies in humans through natural infection is over five years. Previous experiments on llamas immunized with envelope proteins produced broadly neutralizing antibodies with low potency and limited breadth only after more than four months.
These findings indicate that some of the challenges faced in attempts to develop a vaccine for HIV may be due to the limited repertoire of human antibodies. However, the rapid response observed in cows suggests that they may be an ideal model for producing antibodies against other disease-causing organisms to aid the design of a range of vaccines, the authors conclude.