A plant‐based system for rapid production of influenza vaccine antigens

Abstract

Please cite this paper as: Shoji et al. (2011) A plant‐based system for rapid production of influenza vaccine antigens. Influenza and Other Respiratory Viruses 6(3), 204–210. Background Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg‐based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed. Objectives To satisfy the additional global demand for emerging influenza vaccines, high‐performance cost‐effective technologies need to be developed. Plants have a potential as an economic and efficient large‐scale production platform for vaccine antigens. Methods In this study, a plant virus‐based transient expression system was used to produce hemagglutinin (HA) proteins from the three vaccine strains used during the 2008–2009 influenza season, A/Brisbane/59/07 (H1N1), A/Brisbane/10/07 (H3N2), and B/Florida/4/06, as well as from the recently emerged novel H1N1 influenza A virus, A/California/04/09. Results The recombinant plant‐based HA proteins were engineered and produced in Nicotiana benthamiana plants within 2 months of obtaining the genetic sequences specific to each virus strain. These antigens expressed at the rate of 400–1300 mg/kg of fresh leaf tissue, with >70% solubility. Immunization of mice with these HA antigens induced serum anti‐HA IgG and hemagglutination inhibition antibody responses at the levels considered protective against these virus infections. Conclusions These results demonstrate the feasibility of our transient plant expression system for the rapid production of influenza vaccine antigens.

Beads-Based Electrochemical Assay for the Detection of Influenza Hemagglutinin Labeled with CdTe Quantum Dots

“…Influenza type A can be subtyped by different variants of NA (1-9) and HA (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), which differ from each other in virulence, host specificity and binding of HAs subtypes on human and/or avian glycan receptors [19][20][21][22][23][24]. Specific HA-glycan affinity has been exploited as the basis for isolation of various types of influenza viruses [25].…”

“…These days are characterized by rapid population growth, international trade and globalization, and for this reason the risk of influenza pandemics looms larger and larger [1]. Influenza is one of the most frequently occurring respiratory diseases, which causes approximately 500,000 deaths every year.…”

“…Combinations of HA (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and NA (1)(2)(3)(4)(5)(6)(7)(8)(9) subtypes affect the biological properties of influenza viruses, especially their host range and virulence. HA is responsible for the initiation of the infection and it binds sialic acid on the host cell surface.…”

Plant Bioreactors for the Antigenic Hook-Associated flgK Protein Expression

“…It has been found to be extremely versatile for genetic manipulation and tissue culture research (Ganapathi et al, 2004). Several recombinant proteins have been expressed in transgenic tobacco as bioreactors for the production of commercially important pharmaceutical molecules (Shoji et al, 2012). Many immunogenic proteins have been synthesised in tobacco and several plant-based vaccine candidates have demonstrated efficacy against a large number of human and animal pathogens after oral administration (Daniell et al, 2001).…”

Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

“…HA-based influenza vaccines have successfully been developed over the last decade from many sources, including bacterial 17 and plant expression systems. [18][19][20] Regardless of the source, a significant disadvantage is that HA protein is not robustly immunogenic on its own. Most formulations require high doses, repeat immunization, or adjuvant formulation for effective and protective immune activation in animal models 18,21 and in clinical trials.…”