Abstract
Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs). Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA). Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs) against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs.
Highlights
Influenza viruses cause highly contagious respiratory tract infections associated with high morbidity and mortality rates
We recently showed that intranasal immunization of mice with recombinant adenovirus expressing fusion protein consisting of codon-optimized HA2-subunit of A/California/7/2009(H1N1) virus fused to a trimerized form of CD40L completely protected mice against lethal challenges with divergent influenza A subtypes including H1N1, H3N2, and H9N2
One of the major inherent drawbacks of current influenza vaccines is the need for annual reformulation to antigenically match circulating strains
Summary
Influenza viruses cause highly contagious respiratory tract infections associated with high morbidity and mortality rates. There are at least 18 HA (1–18) and 11 NA (1–11) subtypes including the recently isolated highly divergent influenza A viruses from bats (H17N10 and H18N11) [3, 4]. Since 1997, direct transmission of the highly pathogenic avian influenza (HPAI) H5N1 virus from poultry to humans has increased and resulted in high mortality rate [19]. Other avian viruses such as H9N2 [20], H7N7 [21], and H7N9 [22] have been isolated from humans. Human-to-human transmission of these viruses has been limited so far, the ability of these HPAI viruses to infect humans and cause disease as well as their persistent circulation in domestic poultry have raised the concerns about their potential to cause devastating pandemics
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