The severity of the 2017/18 flu season has led to questions of how well this year’s vaccines have worked. In a statement last month, US Food and Drug Administration (FDA) commissioner Scott Gottlieb suggested the efficacy rate was around 25%.
There are a number of reasons behind this, but much of the blame has been put down to the H3N2 influenza strain. Gottlieb suggested traditional egg-based vaccines are less effective against this particular strain, something Maryland-based vaccine developer Novavax explored further in its fourth quarter 2017 financial call this week.
The problem with the H3N2 strain is not new, said CEO Stanley Erck, with vaccine effectiveness estimated to be only 14% over the last five years against this strain.
“Core vaccine effectiveness is a result of the mismatch between the vaccine and current circulating viruses. When you have a mismatch, the immune response stimulated by vaccines may not be protected against the actual viruses that infect us.”
While antigenic evolution is a cause of the mismatch, the issue of egg adaptation in the manufacturing process is “perhaps the biggest culprit in this season's poor vaccine efficacy.”
According to Erck, the same process as has been used for the past 50 years for the production of flu vaccines.
“The manufacturing process starts by identifying the viruses that are infecting humans and then growing them up in chicken eggs. The problem is that viruses which successfully infect humans don't grow well in eggs and have to be modified,” whether intentionally or through changes occurring when scaling up production in millions of eggs.
While there are recombinant flu vaccines commercially available Erck said 87% of commercial flu vaccines in the US are still manufactured by growing flu viruses in eggs.
Novavax is looking to enter the space with its early-phase candidate NanoFlu, which recently demonstrated improved immune response compared with Sanofi Pasteur’s egg-based manufactured vaccine Fluzone.
“NanoFlu is recombinant and allows us to make a vaccine that from a genetic standpoint, exactly matching the virus sequence of the CDC's recommended flu strains,” said Erck.
Novavax president of R&D Greg Glenn added: “The recombinant vaccine contains the exact protein found in wild-type viruses. The egg-based vaccine does not; it was selected for its ability to grow round eggs.”
Like Protein Science’s (now Sanofi’s) commercially available vaccine Flublok, Novavax uses an insect virus-based expression system (in this case the SF9 insect cell baculovirus system) to grow viral hemagglutinin.
But unlike Flubok, NanoFlu is combined with an adjuvant Erck said “stimulates a broader immune response and broader protection that addresses mismatch.”