Abstract
The emergence of new influenza strains causing pandemics represents a serious threat to human health. From 1918, four influenza pandemics occurred, caused by H1N1, H2N2 and H3N2 subtypes. Moreover, in 1997 a novel influenza avian strain belonging to the H5N1 subtype infected humans. Nowadays, even if its transmission is still circumscribed to avian species, the capability of the virus to infect humans directly from avian reservoirs can result in fatalities. Moreover, the risk that this or novel avian strains could adapt to inter-human transmission, the development of resistance to anti-viral drugs and the lack of an effective prevention are all incumbent problems for the world population. In this scenario, the identification of broadly neutralizing monoclonal antibodies (mAbs) directed against conserved regions shared among influenza isolates has raised hopes for the development of monoclonal antibody-based immunotherapy and “universal” anti-influenza vaccines.
Highlights
The outbreak of the highly pathogenic avian influenza (HPAI) H5N1 isolates highlighted how much influenza viruses are still a serious threat for human health
Particular attention is reserved for the avian reservoir, which cannot be efficiently controlled, and at the same time represent an economical problem in case of infections
Even considering a potential transmission route involving an intermediate host, the emergence of viral strains able to infect humans and potentially able to cause pandemics is a chief menace for the human health
Summary
The outbreak of the highly pathogenic avian influenza (HPAI) H5N1 isolates highlighted how much influenza viruses are still a serious threat for human health. The continuous generation of viral antigenic variants (antigenic drift) is the major cause of the seasonal epidemics, and the factor determining the emergence of isolates resistant to currently available anti-influenza drugs (adamantanes and neuraminidase inhibitors) [9,10,11,12]. A pivotal role in the rational design of novel broadly protective approaches can be played by the fine definition of B-cell epitopes on influenza hemagglutinin (HA), widely shared among phylogenetically highly divergent influenza subtypes. This can be achieved by using broadly neutralizing monoclonal antibodies (mAbs) as “molecular probes”. We describe the epitopes of a panel of mAbs endowed with heterosubtypic neutralizing activity and able to target conformational motifs widely shared among influenza isolates
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