Influenza: A Unique Problem in Vaccination

Abstract

The genetic attributes of the influenza virus lead to unique problems in vaccination. First, a highly mutable RNA genome, resulting in sequential antigenic variation, could potentially manifest as a vaccine failure or epidemic influenza. Second, a segmented genome that engenders the virus with the capacity for genetic reassortment and the introduction of new antigens into a host population could possibly result in a pandemic. The core problem in combating influenza is the need for continual vaccine revision and induction of broader heterovariant immunity. Current vaccines – the conventional inactivated vaccine and the live attenuated vaccine – rely on technology of strain selection and production methods that is decades old. The immunity induced by these vaccines is dominated by the response to hemagglutinin (HA) and, therefore, the vaccines are most effective when there is sufficient antigenic relatedness between the vaccine strain HA and the circulating wild-type virus HA. Consequently, these vaccines are susceptible to failure when an antigenically distinct virus emerges after the selection of the vaccine candidate strain. New vaccine strategies need to include immunization with other viral antigens in addition to HA, thereby broadening the immune response against influenza. Inclusion of the more slowly evolving neuraminidase and/or M2e in a vaccine against influenza could reduce the vulnerability to antigenic changes, and conserved antigens from internal proteins – nucleoprotein and M1 – delivered to induce T-cell helper and cytotoxic T cells, could ensure the presence of activated T cells that facilitate clearance of pandemic strains. Alternative production technologies, such as recombinant baculovirus and yeast, and different delivery methods, such as virus-like particles, should be explored to decrease vaccine production times and reduce reliance on embryonated eggs.