Current and next generation influenza vaccines: Formulation and production strategies

Abstract

Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be addressed. We give an overview of the current status and novel developments in the landscape of influenza vaccines from an interdisciplinary point of view. The feasibility of novel vaccine concepts not only depends on immunological or clinical outcomes, but also depends on biotechnological aspects, such as formulation and production methods, which are frequently overlooked. Furthermore, the next generation of influenza vaccines is addressed, which hopefully will bring cross-reactive influenza vaccines. These developments indicate that an exciting future lies ahead in the influenza vaccine field.

A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro

“…Vaccination programs are important for preventing and controlling influenza; however, vaccines lose their efficacy when there is an antigenic mismatch with the circulating viruses (2, 3) or when they are administered to high-risk groups, such as the elderly and very young (4). Therefore, antiviral drugs represent a critical, additional line of defense against seasonal influenza viruses and against emerging subtypes for which no vaccine may be available.…”

Murine polyomavirus VLPs as a platform for cytotoxic T cell epitope-based influenza vaccine candidates

“…Even though Tc-epitope-based vaccine cannot prevent infection due to a prerequisite of pathogen entry into the cell, this type of vaccine can reduce the severity of the disease and prevent further spread of the pathogen in the host (Brown and Kelso 2009). Moreover, Tc-epitope presentation via the MHC Class I and MHC Class II pathways allows targeting of conserved internal proteins of influenza virus, and thus may provide broad protection against heterologous strains, possibly reducing vaccine updating frequency (Milian and Kamen 2015;Soema et al 2015). Thus, it could be used as prepandemic vaccine before conventional vaccine specific to the pandemic strain becomes available (Woolard and Kumaraguru 2010), or between influenza seasons by boosting pre-existing T cell immunity (Gilbert 2012).…”

“…A broadly cross-protective influenza vaccine could reduce updating frequency or provide some level of protection to slow initial stages of a pandemic (Brown and Kelso 2009). This may be achieved by targeting the more conserved internal proteins to stimulate cellular immunity (Houser and Subbarao 2015;Milian and Kamen 2015;Soema et al 2015), by delivering conserved Tc-epitopes into dendritic cells to be presented via the Major Histocompatibility Complex (MHC) Class I pathway (Brown and Kelso 2009;Sette et al 2002;Woolard and Kumaraguru 2010). A versatile delivery system capable of performing this function needs to be developed while maintaining short production time, low production cost, as well as high production capacity.…”

“…Although peptide synthesis is scalable (Bray 2003), the necessary coupling with delivery platform post-synthesis complicates the production and may add to production cost (Soema et al 2015) Another strategy is genetically inserting these peptide sequences into a recombinant carrier protein such as capsid proteins in the form of virus-like particles (VLP), or subunit proteins such as flagellin.…”

“…However, traditional vaccine production takes 4 to 6 months to complete and might not match the newly mutated circulating strain (Milian and Kamen 2015;Soema et al 2015).…”