Abstract
BackgroundThe recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins.ResultsOur data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability.ConclusionWe conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages.
Highlights
The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process
The objectives of this study were (1) to study the properties of the A/California/07/2009 recombinant hemagglutinin (rHA) protein and compare it to other rHA proteins derived from seasonal influenza strains and (2) to develop an understanding of the cause of the instability observed with this antigen
HA0 is cleaved into HA1 and HA2 subunits when treated with trypsin, and we found that A/California/07/2009 rHA was digested into HA1 and HA2 peptides in a similar manner (Figure 5)
Summary
The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The process of preparing a new vaccine seed strain suitable for growth in eggs can be quite lengthy, as it involves re-assortment between the genes of a high yielding donor virus, such as A/Puerto Rico/8/34, and the hemagglutinin (HA) and neuraminidase (NA) genes of the new influenza strain [7]. The candidate seed virus strains are further selected for high growth capability in eggs before they can be used for the production of vaccines. This manufacturing process is lengthy and limited in scalability due to its dependence on the availability of embryonated chicken eggs
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