Conventional influenza vaccines use an egg-based culture and harvest process. This method of production is slow and inflexible, compared with emerging cell-culture based approaches that can respond rapidly to the influenza virus' inherent ability to "drift," or more dangerously, to "shift"—a critical factor that would arise in the event of a pandemic. ImmBio's ImmunoBodies is a breakthrough vaccine under process development at Eden Biodesign that uses a baculovirus expression system for production. The vaccine is constructed from part of the flu hemagglutinin protein fused to the human dendritic cell-binding Fc region of human immunoglobulin, enabling it to efficiently trigger a broad, protecting response. In the event of a new strain tracking out of its protective range, the construct can be rapidly re-engineered. The baculovirus manufacturing capacity also can be augmented to produce large volumes.
ImmunoBiology ("ImmBio"), a biotech vaccine development company in Cambridge, UK, and Eden Biodesign, operating the UK's National Biomanufacturing Centre in Liverpool, are therefore developing an antibody-antigen fusion complex product manufactured in a baculovirus expression system.
The influenza virus belongs to the Orthomyxoviridae family. It is an enveloped RNA virus with a segmented genome consisting of eight single-stranded negative RNA segments. The virus is split into three subtypes: A, B, and C, based on antigenic differences in two of its structural proteins: the matrix protein M2, and the nucleoprotein. As infection with the C subtype is relatively mild, vaccination is typically against the A and B subtypes.
Projecting from the viral envelope is a conglomeration of three proteins: hemagglutinin (HA), neuraminidase (NA), and the matrix (M2) protein. Influenza A viruses are subtyped according to the HA and NA proteins they display on their viral envelope. Although 14 HA proteins and 9 NA proteins have been identified, only a limited number are infectious to humans (H1, H2, H3, N1, and N2). The most common combination currently in circulation is the subtype H3N2. Distinct strains can be further identified by the virus type, geographic origin, and year of isolation.
To cope with this variety, current vaccines are trivalent, with two components against A and one against B. Through the World Health Organization (WHO) surveillance network, which tracks strain changes, manufacturers that supply vaccines to the US and Europe are advised around February what subtypes are expected to be prevalent through the following winter, when influenza incidence is highest. Typically, at least one component must be altered each year. The antigen composition recommended by the WHO may need modification if the strain grows poorly in eggs, a situation that may compromise efficacy. To begin the Northern hemisphere seasonal vaccination program, large volumes of vaccine product need to be available by September.