By focusing on key parts which remain stable over time, scientists have created a universal flu vaccine that offers broad cross protection against different strains and subtypes of influenza A viruses in both young and old populations, according to a new study reported in npj Vaccines.
The researchers developed the universal flu vaccine by genetically linking two highly conserved portions of the virus: the extracellular domain of matrix 2 (M2e) and the stalk protein found in influenza A H3N2 viruses. The findings show that vaccinating against M2e-stalk protein induced broad protection against different influenza virus strains and subtypes by universal vaccine-mediated immunity in adult and aged mice.
Developing effective influenza vaccines has been a challenge because the head portion of the influenza virus is constantly mutating. When comparing the H1N1 and H3N2 influenza A viruses, particular challenges exist in H3N2 subtypes because of stalk mutations in circulating strains and the unstable structure of stalk proteins for H3N2 viruses. These drawbacks have been difficult to overcome in developing effective H3 stalk-based vaccines.
In the past decade, vaccine effectiveness against H3N2 hovered around 33%, and during the 2014–2015 flu season, it dropped to 6%. New mutations of H3N2 variants emerged with increased virulence. Also, the outbreak of H7N9, another influenza A subtype, caused concern for potential pandemics. Therefore, developing an effective vaccine to protect against these viruses is a high priority.
“The M2e-stalk protein, for the first time, could be easily produced in bacterial cell cultures at high yields and was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2 and H7N9) at similar levels in adult and aged mice,” said Dr Sang-Moo Kang, senior author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. “These results provide evidence that M2e-stalk genetic fusion proteins can be produced in a large scale at low cost and developed as a universal influenza A virus vaccine candidate for young and aged populations.”
The study found this novel M2e-stalk protein vaccine induced M2e and stalk-specific Immunoglobulin G (IgG) antibodies that recognised antigenically diverse influenza viral antigens on virus particles and on the infected cell surface. The vaccine also stimulated protective cellular T cell immunity and effective lung influenza viral clearance in mice.
Source: Georgia State University
