The prospects and challenges of universal vaccines for influenza

Abstract

Vaccination is the most effective way to reduce the impact of epidemic as well as pandemic influenza. However, the licensed inactivated influenza vaccine induces strain-specific immunity and must be updated annually. When novel viruses appear, matched vaccines are not likely to be available in time for the first wave of a pandemic. Yet, the enormous diversity of influenza A viruses in nature makes it impossible to predict which subtype or strain will cause the next pandemic. Several recent scientific advances have generated renewed enthusiasm and hope for universal vaccines that will induce broad protection from a range of influenza viruses.

Hemagglutinin Stalk Immunity Reduces Influenza Virus Replication and Transmission in Ferrets

“…HA-specific universal influenza virus vaccines shift humoral immune responses toward the antigenically conserved but immunosubdominant HA stalk region, thereby overcoming these limitations. Such a vaccine could confer protection against homologous and drifted influenza virus strains, eliminate the requirement for reformulation of annual influenza virus vaccines, and confer increased protection against influenza viruses with pandemic potential (6)(7)(8). To investigate the level of protection conferred by HA stalk-based immunity against infection by influenza viruses, we tested a universal influenza vaccine approach in the ferret model.…”

Significant Replication Time-points of Avian Influenza A Virus Strain H5N1 in Madin-Darby Canine Kidney Cells

“…AIV H5N1 M2 gene is highly conserved (Subbarao & Matsuoka 2013) and hence suitable to be used in virus detection using PCR. To ensure the accuracy and validity of M2 gene amplification, the total RNA extracted from both the media and MDCK cells were normalised to 38 ng/µl, which was also the lowest concentration among the collected samples.…”

“…The virus causes death and illness in domestic and migratory birds, as well as vulnerable human beings (Subbarao & Matsuoka 2013;Hatta et al 2011).…”

High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity

“…Given that the HA antigen often continues to mutate (including antigenic drift and shift), the choice of vaccine strain should also result in a corresponding change; otherwise, the vaccine prevention effect cannot be assured, even without much effect (2)(3)(4). Inactivated vaccines produced in embryonated hen eggs have several serious disadvantages (e.g., egg supply, matching vaccine strains, unwanted antigenic variants, and contamination with egg derived protein) that may decrease vaccine efficiency (5). Ideally, a flu vaccine should contain epitopes conserved in all influenza isolates to be effective against all strains of influenza A (6).…”

“…Passive immunization with these antibodies has reduced viral replication in the lungs of mice infected with influenza A virus (9). Therefore, the development of a universal influenza vaccine that can provide crossprotective effect against different subtypes has attracted considerable research interest (10)(11)(12). M2e is poorly immunogenic during natural infection (13).…”