Abstract
Every year, influenza virus infections cause significant morbidity and
mortality worldwide. They pose a substantial burden of disease, not only
in terms of health but also economic-wise. Owing to the ability of
influenza viruses to continuously evolve, annual seasonal influenza
vaccines are necessary as a prophylaxis. However, current influenza
vaccines against seasonal strains have limited effectiveness and require
yearly reformulation due to the virus undergoing antigenic drift or
shift. Vaccine mismatches are common, conferring suboptimal protection
against seasonal outbreaks, and the threat of the next pandemic
continues to loom. Therefore, there is a great need to develop a
universal influenza vaccine (UIV) capable of providing broad and durable
protection against all influenza virus strains. In the quest to develop
a UIV that would obviate the need for annual vaccination and
formulation, a multitude of strategies are currently underway. Promising
approaches include targeting the highly conserved epitopes of
hemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e),
and internal proteins of the influenza virus. The identification and
characterisation of broadly neutralising antibodies (bnAbs) targeting
conserved regions of the viral HA protein, in particular, have provided
important insight into novel vaccine designs and platforms. This review
discusses universal vaccine approaches presently under development, with
an emphasis on those targeting the highly conserved stalk of the HA
protein, recent technological advancements used, and the future
prospects of a UIV in terms of its advantages, developmental obstacles
and potential shortcomings.