Paul-Ehrlich-Institut

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Towards universal flu vaccines?

The flu epidemic in Germany in 2017/18 was unusually severe, with more than 1,600 deaths. Scientists are urgently searching for an effective flu vaccine that no longer requires annual updates.

Influenza Virus Influenza Virus Source: K. Boller / PEI

Seasonal flu epidemics are caused by different strains of influenza virus that are divided into subtypes A and B. Influenza viruses differ, among other things, in their surface proteins haemagglutinin and neuraminidase. Vaccination is the best protection against influenza infection. However, the virus subtypes in circulation vary each year and may acquire additional mutations over time. For this reason, each spring the World Health Organization (WHO) predicts which influenza subtypes are likely to be circulating in the forthcoming winter season.

Flu vaccines then contain antigens – surface elements of the virus that trigger an immune response – of the three or four subtypes that are expected to be most prevalent. The currently licensed inactivated flu vaccines primarily target the immune response to the haemagglutinin antigen. This antigen is highly variable, often changing its surface structure even in the course of a single flu season, which may reduce the efficacy of the vaccines.

The situation is different with the other surface protein, neuraminidase, since it is generally conserved more. Researchers from the Paul-Ehrlich-Institut led by Prof. Veronika von Messling, head of the Veterinary Medicine division until September 2018, in collaboration with the German Centre for Infection Research (DZIF) and the Institute of Virology and Immunology in Mittelhäusern, Switzerland, investigated whether the neuraminidase protein can also trigger an immune response that contributes to protection. They used the vesicular stomatitis virus (VSV) as a vaccine vector and carrier of the genetic information of haemagglutinin and neuraminidase antigens. They then tested the immune response in mice and ferrets to both antigens from various strains of influenza virus.

The result: animals that had been vaccinated against neuraminidase were equally well protected against challenge with a matched virus as animals whose vaccination had been targeted at the haemagglutinin protein. The neuraminidase-based vaccines even resulted in immunity to influenza viruses with a different haemagglutinin subtype (cross-protection), as long as they carried the same neuraminidase subtype. The extent of this protection could be predicted by the detection of specific antibodies in the animals.

Publication

Walz L, Kays SK, Zimmer G, von Messling V (2018): Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype.
J Virol 92: e01006-18.
Online-Abstract

Updated: 31.10.2019