Abstract
Current influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the context of an emerging pandemic strain. Here we explore the production of recombinant influenza haemagglutinin using the ciliated protozoan Tetrahymena thermophila. For the first time we were able to produce haemagglutinin from both seasonal influenza A and B strains. This ciliate derived material was immunogenic, inducing an antibody response in both mice and non-human primates. Mice immunized with ciliate derived haemagglutinin were protected against challenge with homologous influenza A or B viruses. The antigen could also be combined with submicron particles containing a Nod2 ligand, significantly boosting the immune response and reducing the dose of antigen required. Thus, we show that Tetrahymena can be used as a manufacturing platform for viral vaccine antigens.
Highlights
Influenza infections are one of the most common causes of primary care consultation and represent an important economic burden worldwide [1]
A variety of polymers exists from which particles for drug delivery can be prepared, of which poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) are the most commonly studied [33]
PLA and PLGA have been extensively studied for vaccine formulation with a body of literature demonstrating their advantages for antigen delivery
Summary
Influenza infections are one of the most common causes of primary care consultation and represent an important economic burden worldwide [1]. The World Health Organization (WHO) estimates influenza epidemics to result in about 3 to 5 million cases of severe illness globally each year, leading to 290,000 to 650,000 deaths. Annual influenza vaccination is considered by the WHO to be the most effective strategy to prevent disease caused by the influenza A and B viruses currently co-circulating in humans. Vaccination is recommended for people aged over 18 years in the USA, and over 65 in most of European States [2]. Egg-based influenza vaccine production is complex to scale up and work intensive, taking several months following the isolation of new strains. Growth of viruses in eggs may lead to a selection pressure, altering antigenicity [4], for the heavily humanized H3N2 strains [5]
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