Broadly neutralizing antibodies (bNAbs) have inspired vaccines against highly variable pathogens, most notably recently in HIV. A team led by Scripps Research Institute scientists, with participation from Janssen researchers among others, has applied that idea—with a little twist—to developing a universal flu vaccine from llamas.
Developed based on what are called broadly neutralizing single-domain antibodies (sdAbs) isolated from llamas immunized with flu vaccines, the therapy can potentially combat almost all influenza viruses for at least an entire flu season, the team reported in the journal Science.
Currently, seasonal flu vaccines have many limitations. Selected vaccine strains may not match the actual circulating viruses, leading to reduced effectiveness. They also tend to be least protective in those who are most vulnerable to influenza such as the elderly. Plus, they must be updated each season and cannot be used against pandemic strains such as the H1N1 swine flu.
That’s why scientists and biopharma companies big and small are turning to universal flu vaccines, considered the “holy grail” of flu research. While seasonal flu vaccines target the virus’s hemagglutinin head, which undergoes mutations frequently, bnAbs can bind to the highly conserved hemagglutinin stem region, which usually remains unchanged. Therefore theoretically, bnAbs are ideal candidates to fight multiple strains.
Several bnAbs have been developed against influenza, but they lack cross-strain coverage against both influenza A and B and may require multiple high-dose injections throughout the flu season to maintain protection, according to the team.
For their candidate, the Scripps-led team first immunized llamas with flu vaccines. Then the researchers isolated four sdAbs from the llamas’ blood and linked them together into a multidomain antibody dubbed MD3606.
Unlike most antibodies, sdAbs only have heavy chains and no light chains. They were first discovered in camelids, a family of animals that includes llamas and camels. They are not exactly a new idea. Ablynx, which was recently bought by Sanofi, is developing dozens of sdAbs—also called “nanobodies”—for a wide range of diseases. Their first sdAbs-based drug, Cablivi, has just been approved by European regulators to treat a rare blood-clotting disorder called acquired thrombotic thrombocytopenic purpura. Researchers at the University of California at Riverside have also modified llama antibodies to fight cancer.
Administered intranasally to mice with an adenovirus vector that carries the gene encoding the novel antibody, the Scripps therapy protected the animals against almost all influenza A and B viruses, the team reported. And it appeared to be more powerful than an existing bnAb and those sdAbs it’s based on, according to the team.
Of course, these are only preclinical findings, but if they can be translated into humans, “AAV9.MD3606h may provide passive protection for the entire influenza season and would be of particular benefit to the elderly and other high-risk groups,” the authors wrote in the study.