Universal influenza vaccination: Future prospects

Abstract

The current influenza vaccines only contain the complete haemagglutinin (HA) of influenza as only immunogen determining a little lasting immunity. This phenomenon is due to the fact that they are based almost exclusively on inducing an immune response against the globular domain (head) of the HA (subunit HA1), since it has been observed that it constitutes the viral immunodominant antigen because it presents on its surface the majority of variable epitopes (glycosylation patterns). However, because it is the most accessible and external area of ​​the virus, which determines the binding to the cellular receptor, it is the one that presents a higher rate of antigenic variability or diversity due to the intense selective pressure of the human immune system. Therefore, the WHO has developed a strategic plan for obtaining a universal vaccine against influenza that is characterized by being able to be applied in all age groups and immunosuppressed and that especially uses as an immunogen a conserved influenza protein that maintains the protection less for a long period of time. Multiple vaccine platforms have been developed but at present it seems that those based on the induction of progressive immunity against the conserved antigens of the HA stem (HA2) present a more hopeful future. Chimeric HA (cHA) with a stem common to a certain subtype and heads belonging to unusual subtypes have been constructed with this stem. The progressive immunization with them increases and reinforces the immunity against the stem showing cross reaction with all those belonging to the same genetic groups (H1 or H2), obtaining a protection almost similar to the classic vaccine based on complete HA. Clinical trials that are underway with these chimeric vaccines will indicate whether the human response induced by them will be sufficient to protect against all known subtypes and if this protection will also be durable and stable.