Toward a broadly protective influenza vaccine

Abstract

The current inactivated influenza virus vaccines induce antibodies that protect against closely related virus strains. They do not, however, protect against antibody-escape variants of seasonal influenza A viruses or new pandemic influenza A viruses emerging from non-human reservoirs. Might boosting influenza A virus-specific CD8+ T cell memory diminish the danger posed by these variant viruses? Pre-existing CD8+ T cell-mediated immunity directed at peptides from conserved internal proteins of the influenza A virus does not prevent infection, but it can promote early virus clearance and decrease morbidity in mice. In this issue of the JCI, Lee et al. show that people who have not been exposed to avian influenza A (H5N1) viruses have cross-reactive CD8+ T cell memory to a wide range of H5N1 peptides (see the related article beginning on page 3478). These peptides could be used to add a CD8+ T cell component to current antibody-focused vaccine strategies with a view to reducing the impact of infection with novel influenza A viruses.

Figure 1. The CTL response to influenza A virus infection.

Influenza A viruses rapidly grow to very high titers in the lungs of infected mice (primary virus growth). Virus clearance is only enhanced (secondary virus growth) by approximately 2–3 days (21) in those animals that have memory CD8⁺ CTL numbers at what might be considered normal, physiological prevalence (<0.5% in spleen). Boosting those CTL counts (to >5%) a few weeks before viral challenge by some form of secondary stimulation can cause the period before the virus is successfully eliminated to be shortened by 48 hours or more (tertiary virus growth) (22). As shown in this issue of the JCI in the study by Lee et al. (14), most people already possess memory CTLs specific for the influenza A viruses. In the face of a rapidly emerging seasonal influenza epidemic, or a pandemic caused by a novel influenza A virus, a possible future strategy to mitigate the impact would be to stockpile a vaccine for emergency use that increases CD8⁺ CTL numbers.