An Improved Inactivated Influenza Vaccine with Enhanced Cross Protection

Frontiers in Immunology
Yawei NiIan Tizard

Abstract

Current inactivated influenza vaccines are strain-specific and poorly effective against variant or mismatched viruses. They are standardized based on their hemagglutinin (HA) or ability to induce strain-specific hemagglutination inhibition (HAI) antibodies. The HA is known to undergo major conformational changes when exposed to the low pH environment of endosomes (pH 5.0 and 37°C), which are required for membrane fusion during virus cell entry. In an effort to improve these vaccines, influenza antigens treated under various low pH conditions were evaluated for increased cross-reactive antibody response and cross protection. It was found that a full range of structural and antigenic changes in HA could be induced by varying low pH treatment conditions from the mild (low pH at ≤25°C) to the strong (low pH at ≥37°C) as determined by analysis of potency, HA morphology, protease sensitivity, and reactivity with an anti-HA2 domain (CD) antibody. Inactivated antigens of both H1N1 and H3N2 strains treated at mild low pH conditions (0-25°C) exhibited only moderate HA structural and antigenic changes and markedly increased antibody response against HA2, the highly conserved part of HA, and cross protection against heterologous challenge ...Continue Reading

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Methods Mentioned

BETA
ELISA
electron microscopy

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