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Vol. 20. Issue 2.
Pages 72-81 (July - December 2019)
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Vol. 20. Issue 2.
Pages 72-81 (July - December 2019)
Review article
DOI: 10.1016/j.vacune.2019.10.002
Universal influenza vaccination: Future prospects
Vacunación antigripal universal: perspectivas de futuro
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J. Reinaa,
Corresponding author
jorge.reina@ssib.es

Corresponding author.
, N. Reinab
a Virology Unit, Hospital Universitari Son Espases, Faculty of Medicine, Universitat de les Illes Balears, Palma, Island of Mallorca, Spain
b Faculty of Medicine, Universitat de Girona, Girona, Spain
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Table 1. Differences between antibodies formed against the two structural constituents of flu haemagglutinin.
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.

Keywords:
Influenza
Universal vaccine
Hemagglutinin
Resumen

Las vacunas antigripales actuales solo contienen como inmunógeno a la hemaglutinina (HA) gripal completa determinando una inmunidad poco duradera. Este fenómeno se debe a que se basan casi exclusivamente en inducir una respuesta inmune frente al dominio globular (cabeza) de la HA (subunidad HA1), ya que se ha observado que constituye el antígeno inmunodominante viral por presentar en su superficie la mayoría de los epítopos variables (patrones de glicosilación). Sin embargo por ser la zona mas accesible y externa del virus, la que determina la unión al receptor celular, es la que presenta una mayor tasa de variabilidad o diversidad antigénica debido a la intensa presión selectiva del sistema inmune humano. Por ello la OMS ha desarrollado un plan estratégico para la obtención de una vacuna universal frente a la gripe que se caracterice por poder ser aplicada en todos los segmentos de edad e inmunodeprimidos y que especialmente utilice como inmunógeno una proteína conservada gripal que mantenga la protección al menos durante un largo período de tiempo. Se han desarrollado múltiples plataformas vacunales pero en estos momentos parece que las basadas en la inducción de inmunidad progresiva frente a los antígenos conservados del tallo de la HA (HA2) presentan un futuro mas esperanzador. Con este tallo se han construido HA quiméricas (cHA) con un tallo común a un determinado subtipo y cabezas pertenecientes a subtipos poco habituales. La inmunización progresiva con ellas incrementa y refuerza la inmunidad frente al tallo mostrando reacción cruzada con todos los pertenecientes a los mismos grupos genéticos (H1 o H2), obteniendo una protección casi similar a la clásica vacuna basada en la HA completa. Los ensayos clínicos que están en marcha con estas vacunas quiméricas nos indicaran si la respuesta humana inducida por ellas será suficiente para protegernos frente a todos los subtipos conocidos y si además esta protección será duradera y estable.

Palabras clave:
Gripe
Vacuna universal
Hemaglutinina

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