PANDEMICS IN THE AGE OF PLANT-TECH: Prospects of Plant-Derived Pandemic Influenza Vaccine

Abstract

The 2009 H1N1 pandemic illustrated the inadequacies of current hen egg-derived production of influenza vaccine. Slow speed and low scalability of egg-based vaccine manufacture postponed vaccination campaigns until the pandemic began to decay by its own accord. Had 2009 H1N1 exhibited higher transmissibility or virulence, the global human cost of the delays in egg-based vaccine production would have been catastrophic. Fortunately, the 2009 H1N1 pandemic spurred development towards next-generation influenza vaccines. In particular, plant-derived influenza vaccines have demonstrated strong promise. Plant-derived vaccines tout exceptional production speed, scalability, and low cost. With their purported surge capacity, plant-derived vaccines could curb epidemics early and stamp out pandemics therein. Plant-derived vaccines, however, have been substantially less immunogenic than influenza vaccines produced in eggs or competing recombinant systems. To overcome this deficiency, our literature review indicates monoglycosylation, trimerization, and VLP formation could increase plant-derived vaccine immunogenicity by 2, 3, and 4-fold respectively. Although none of these molecular techniques by themselves are sufficient to make plant-derived HA immunogenicity competitive with egg-derived or recombinant influenza vaccines, implementing these techniques in tandem may aggregate effects. Even if plant-derived influenza vaccine were immunogenic, however, our modeling studies indicate plant-derived vaccines would not improve pandemic public health outcomes in any significant way. Delays in public processes in pandemic vaccine production—namely reagent preparation and virus detection—constrain plant-derived vaccine production to the same production time as egg-derived vaccines. Only after reform of these public processes can the spectacular mitigating potential of plant derived influenza vaccines become realized. Nevertheless, even under best-case conditions, we find plant-derived vaccines may prove ineffective against highly transmissible and virulent influenza strains.

In light of these findings we propose four policy recommendations: 1. To U.S. HHS: Prioritize funding to BARDA and the FDA to develop rapid methods for preparing reagents to test vaccine. 2. To U.S. HHS: Prioritize funding to CDC and USDA to develop an influenza surveillance network that is rapid, global, and surveys human and animal flu. 3. To plant-derived pandemic influenza vaccine companies: Prioritize immunogenicity research and evaluate prospects of creating seasonal vaccine markets in the developing world. 4. To public health policymakers: Evaluate alternatives to pandemic vaccine-based mitigation strategies.