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Review
. 2014;2014:267594.
doi: 10.1155/2014/267594. Epub 2014 Sep 22.

Passive Broad-Spectrum Influenza Immunoprophylaxis

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Free PMC article
Review

Passive Broad-Spectrum Influenza Immunoprophylaxis

Cassandra M Berry et al. Influenza Res Treat. .
Free PMC article

Abstract

Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics. Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals. However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance. The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest. Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks. Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic. Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.

Figures

Figure 1
Figure 1
Signal transduction pathway for type I IFNs and a summary of key ISG effects on the virus and mucosal immune response during influenza. Type II IFN (IFN-γ) binds IFNGR1 and IFNGR2 heterodimer receptor on the cell surface, which leads to activation of JAK1 and JAK2, STAT dimerization, and phosphorylation with transcriptional activation of ISGs with the GAS element. Type III IFNs (IFN-λ1, -λ2, and -λ3) signal via ligand binding to IFNLR1 and IL-10R2 subunits of the cell surface receptor, activation of JAK1 and Tyk2 with similar downstream signaling pathways as the type I IFNs. ISGs can be either discrete or common sets for the different IFN families. Biological properties of type I, type II, and type III IFNs as identified in T and B cells [–39] do not represent an exhaustive list.
Figure 2
Figure 2
Activities of neutralizing antibodies to influenza virus induced by B cell stimulation. Influenza virus stimulates B cell responses through a sequential process of activation, proliferation, isotype-switching, affinity maturation and selection of antibodies, and memory. The major activities of neutralizing antibody types to viral HA are shown in the inset box [13]. HA-specific antibodies are highly functional and prevent virus infection resulting in less cells being infected in vivo.
Figure 3
Figure 3
Modeling of the impact of prophylaxis on mortality curves during pandemic influenza. Prophylaxis could protect against both morbidity and mortality rates by lowering the number of cases. Effective passive immunity is important to provide coverage during the first wave or six-month risk period of the pandemic whilst an effective vaccine is developed for the identified virus to induce active immunity.

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