INFLUENZA VACCINES: A Conference Report

THIRD INTERNATIONAL CONFERENCE ON INFLUENZA VACCINES FOR THE WORLD, 27 – 30 APRIL 2009, CANNES, FRANCE

 REPORT by Dr Elizabeth Mortimer

Subinit Vaccine Group, UCT

 In general, the conference encompassed a wide array of subjects which included pandemic awareness and strategies, antiviral development and stockpiling, socio-economic implications, clinical safety trials of seasonal and H5N1 vaccines, influenza virus evolution, new techniques including antigenic cartography, new vaccine production systems (plant-produced and virus-like particle (VLP)-based vaccines) and novel adjuvant developments. Pharmaceutical companies also used the conference as a platform to discuss their own products via satellite symposiums for example ‘Novartis’ discussed their promising and safe adjuvant MF59® while ‘Sanofi Pasteur’ introduced their new micro-injection intra-dermal vaccine.

Influenza virus

Influenza virus

Speakers like John Oxford (Retroscreen Virology Ltd, UK) and David Fedson (Independent, France) highlighted the fact that an influenza pandemic is imminent (as currently underscored by the H1N1 influenza outbreak). John Oxford specifically discussed the 1918 pandemic and the lessons to be learned from it. John Oxford discussed general pandemic preparedness and global vaccine demand. Approximately 12% of the world’s countries produce influenza vaccines and these countries use 55-60% of the global vaccine demand. It was reiterated that during a pandemic, the remainder of countries especially the developing countries will struggle to get hold of newly produced pandemic vaccine stock. This will eventually lead to a global political crisis. Therefore, the need to use cell-based (tissue culture) instead of the egg-based vaccines for rapid up-scaling of pandemic vaccine production was considered essential. The importance of developing and including adjuvants in vaccine stocks was also discussed during the conference, especially by Derek O’Hagan (Novartis vaccines, USA), Alex von Gabain (Intercell AG, Austria) and Horoshi Kido (University of Tokushima, Japan). Most speakers suggested that pre-pandemic preparedness by stockpiling is necessary, while some argued that the focus should be on vaccinating live stock (for example against H5N1) to limit outbreaks in the human population. For H5N1 prepandemic preparedness, ‘Novartis’ also presented and discussed the efficacy of their AFLUNOV® (A/Vietnam/1194/2004) and AFLUNOV®-like (A/turkey/Turkey/1/2005) vaccines containing the MF59® adjuvant (oral and numerous poster presentations).

 When considering seasonal influenza vaccines, clinical trials from vaccines produced in various countries were discussed. Vaccines were compared (LAIV versus TIV) as well as their administration (intramuscular versus intranasal). Some speakers, for example Kristen Nichol (University Minnesota, USA) remarked on vaccines specifically designed for the elderly, while Peter Richmond (Western Australia Department of Health, Australia), discussed influenza vaccines for children. The current seasonal influenza vaccine deficiencies were discussed by Arnold Monto (University of Michigan, USA), which include the overestimation of the efficacy of vaccines, the breadth of protection, the duration of protection and needle administration. Most speakers agreed that there is room for improvement and that vaccines that are currently FDA approved (USA), are designed for the individual rather than for the population.

 The topics that were of specific of interest to me were plant-based and VLP-based vaccines. Plant-based vaccines are cheap and can quickly be scaled-up, which are major advantages when a pandemic strikes. Vidadi Yusibov (Fraunhofer USA, USA) presented his group’s plant-based subunit vaccines based on various seasonal and pandemic influenza strains. Yusibov’s group specialised in large scale transient Agro-infiltration of tobacco plants using launch vectors that target recombinant protein expression to the endoplasmic reticulum (ER), to avoid complex glycosylation. They investigated glycosylation of plant-produced recombinant proteins like haemagglutinin (HA) and it was found to be correctly glycosylated and should therefore be safe for human vaccines. Their plant-produced HA vaccine will enter phase I human trials later this year (2009). In addition, this group proved that when the Brisbane H3N2 influenza strain that killed a number of children in Australia was published, they were able to design the sequence, optimise and produce purified HA (800mg/kg plant tissue) within 36 days of announcement. They proved that plant-based vaccines can be produced at a faster rate than traditional egg-based vaccines that can take up to 6 months to produce.

 Nathalie Landry’s group (Medicago Inc, Canada) also focussed on plant-produced vaccines, specifically VLPs containing HA. These self-assembled particles of HA bud out of the plasma of plants. VLPs based on the H5N1 strain were purified by conventional methods (ion exchange) and tested in mice and ferrets. The plant-based vaccine was able to elicit a humoral and cellular immunity in these animals. They are going to do a phase I human trial in August 2009 with 48 subjects.

 When considering other VLP-based vaccines, Ted Ross (University of Pittsburgh, USA) discussed a vaccine that was based on the 1918 H1N1 virus which caused 20 – 50 million deaths worldwide. HA and neuraminidase (NA) were incorporated into a lentiviral core (HIV Gag particles). The intranasally administered VLPs protected mice and ferrets against lethal virus challenge. It was also shown that the vaccine was cross-protective against other strains found in the same phylogenetic clade. Martin Bachman (Cytos Biotechnology, Switzerland) discussed VLPs containing the ectodomain of the matrix 2 protein (M2e) or partial HA proteins of various seasonal influenza strains. These VLPs were expressed via insect cells (baculovirus-mediated) and Escherichia coli and were shown to be protective.

 Lastly, a very interesting poster presentation by Kenny Roose (Ghent University, Belgium) depicted a vaccine that mimics the natural tetrameric structure of influenza M2e. M2e was fused to a modified form of yeast transcription factor’s leucine zipper domain which resulted in four chain coiled coils. This vaccine was able to elicit antibodies that were specific to the natural tetrameric M2e and protected mice against lethal challenge with H3N2 and H1N1.

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