NIAID CEIRS | Research Publication Commentary
The seasonal flu vaccine is reformulated each year to protect against influenza strains that are expected to prevail in the upcoming flu season. Because sufficient quantities of influenza vaccine can take at least six months to manufacture, the strains selected for production are chosen ahead of the flu season. Traditional flu vaccines have been designed to protect against three influenza viruses (trivalent vaccine) – two influenza A (H1N1 and H3N2) viruses and only one influenza B (B/Victoria or B/Yamagata) virus. Neutralizing antibodies cross-react poorly across the two influenza B lineages, so if the circulating influenza B strain is not the one chosen for the vaccine, then vaccine efficacy will likely be compromised. Moreover, small changes are occasionally introduced into the virus (antigenic drift), which can result in a mismatch between strains selected for the vaccine and those that are circulating, contributing to reduced vaccine efficacy as vaccines generate neutralizing antibodies that are strain specific. Thus, there remains a need to identify additional correlates of protection necessary to develop broadly-protective vaccines.
Previous research has shown that CD8+ cytotoxic T lymphocytes (CTLs) reduce viral replication and promote viral clearance by identifying and destroying virus-infected cells. In fact, several studies have demonstrated that influenza A virus-specific CTLs contribute to immunity against antigenically different strains. To identify additional mechanisms to protect against influenza B viruses, Carolien E. van de Sandt and colleagues at the Erasmus Medical Center investigated the cross-reactivity of influenza B virus-specific CTLs to two opposing lineages of influenza B virus. The researchers demonstrate that influenza B virus-induced CTLs are cross-reactive between and within the distinct B/Victoria and B/Yamagata lineages, suggesting that the immune response elicited by one lineage can protect against the other. The success of CTLs in protecting across distinct lineages is believed to be due to the conserved epitopes contained in the internal proteins present in the two distinct influenza B lineages, allowing for cross-reactivity.
These findings suggest that influenza B virus-specific CTLs may offer some protection against both influenza B lineages as well as those influenza B strains that have undergone antigenic drift. Although CTLs ameliorate disease rather than protect against infection, induction of CTLs appears to be a promising mechanism to add broad protection to vaccines against influenza viruses.