Abstract
Influenza virus still represents a considerable threat to global public health, despite the advances in the development and wide use of influenza vaccines. Vaccination with traditional inactivate influenza vaccines (IIV) or live-attenuated influenza vaccines (LAIV) remains the main strategy in the control of annual seasonal epidemics, but it does not offer protection against new influenza viruses with pandemic potential, those that have shifted. Moreover, the continual antigenic drift of seasonal circulating influenza viruses, causing an antigenic mismatch that requires yearly reformulation of seasonal influenza vaccines, seriously compromises vaccine efficacy. Therefore, the quick optimization of vaccine production for seasonal influenza and the development of new vaccine approaches for pandemic viruses is still a challenge for the prevention of influenza infections. Moreover, recent reports have questioned the effectiveness of the current LAIV because of limited protection, mainly against the influenza A virus (IAV) component of the vaccine. Although the reasons for the poor protection efficacy of the LAIV have not yet been elucidated, researchers are encouraged to develop new vaccination approaches that overcome the limitations that are associated with the current LAIV. The discovery and implementation of plasmid-based reverse genetics has been a key advance in the rapid generation of recombinant attenuated influenza viruses that can be used for the development of new and most effective LAIV. In this review, we provide an update regarding the progress that has been made during the last five years in the development of new LAIV and the innovative ways that are being explored as alternatives to the currently licensed LAIV. The safety, immunogenicity, and protection efficacy profile of these new LAIVs reveal their possible implementation in combating influenza infections. However, efforts by vaccine companies and government agencies will be needed for controlled testing and approving, respectively, these new vaccine methodologies for the control of influenza infections.
Highlights
Influenza A Virus (IAV) carrying rearranged genomes have shown to serve as live-attenuated influenza vaccines (LAIV) candidates offering several advantages over other LAIV approaches: (i) because of the reorganization of the genome, it is unlikely, if not impossible, for the virus to revert to WT; (ii) foreign genes could be expressed by altering the viral genome organization without altering protein expression; (iii) the reorganization of the viral genome does not affect the antigenicity of viral proteins; and, (iv) rearranged viruses expressing additional HA
The LAIV was approved for use during the 2018–2019 influenza season, the reduced effectiveness of the quadrivalent LAIV remains unknown
This highlights the urgent and pressing medical need of new approaches to generate more effective LAIVs that are capable of preventing or ameliorating the effects of seasonal and/or pandemic influenza by providing broader and more long-lasting immune protection than that elicited by current vaccines
Summary
IAV belongs to the Orthomyxoviridae family of enveloped negative sense, single-stranded RNA viruses with a segmented genome [1] (Figure 1). The inner surface envelope matrix 1 (M1) protein encloses the viral ribonucleoprotein (vRNP) complexes These vRNPs present the core of the virion and consist of the viral (v)RNA segments that are coated with viral nucleoprotein (NP), and one single copy of the viral heterotrimeric polymerase complex that is made up of the polymerase acidic (PA) and basic 1 and 2 (PB1, PB2). Synthesized vRNPs need to be exported from the nucleus to the cytoplasm and transported to the cell surface in order to be packaged into the new viral particles In this regard, the assembly of a nuclear export complex consisting of vRNP, M1, and the nuclear export protein (NEP), which contains two nuclear export signals, is required [17,18]. Lines) recognized by the viral RdRp for viral genome replication and gene transcription
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