Scientists have developed a new technique for vaccine design that they say could be particularly useful against HIV and other fast-changing viruses.
The study offers a step toward solving what has been one of the central problems of modern vaccine design: how to stimulate the
immune system to produce the right kind of antibody response to protect against a wide range of viruses.
The team led by scientists from The Scripps Research Institute (TSRI) and the International AIDS Vaccine Initiative (IAVI)demonstrated their new technique by engineering an immunogen (substance that induces immunity) that has promise to reliably initiate an otherwise rare response effective against many types of HIV.
"We're hoping to test this immunogen soon in mice engineered to produce human antibodies, and eventually in humans," said team leader William R Schief in the study published in the journal Science Express.
For highly variable viruses such as HIV and influenza, vaccine researchers want to elicit antibodies that protect against most or all viral strains - not just a few strains, as seasonal flu vaccines currently on the market.
Vaccine researchers have identified several of these broadly neutralising antibodies from long-term HIV-positive survivors, harvesting antibody-producing B cells from blood samples and then sifting through them to identify those that produce antibodies capable of neutralising multiple strains of HIV.
Such broadly neutralising antibodies typically work by blocking crucial functional sites on a virus that are conserved among different strains despite high mutation elsewhere.
However, even with these powerful broadly neutralising antibodies in hand, scientists need to find a way to elicit their production in the body through a vaccine.
"For example, to elicit broadly neutralising antibodies called VRC01-class antibodies that neutralise 90% of known HIV strains, you could try using the HIV envelope protein as your immunogen," said Schief in a statement.
To reliably initiate that VRC01-class antibody response, Schief and his colleagues therefore sought to develop a new method for designing vaccine immunogens.
Researcher Joseph Jardine evaluated the genes of VRC01-producing B cells in order to deduce the identities of the less mature B cells - known as germline B cells - from which they originate.
Germline B cells are major targets of modern viral vaccines, because it is the initial stimulation of these B cells and their antibodies that leads to a long-term antibody response.
Several iterative rounds of design and selection using a panel of germline antibodies produced a final, optimised immunogen - a construct they called eOD-GT6.