When we experience a particularly bad flu season, like the current one, the question of how a single disease can vary so wildly is often raised. The answer lies in the simple fact that the virus copies its RNA genome with very poor accuracy which means that the virus is constantly mutating and evolving to evade our immune systems and the vaccines we develop.
Designing vaccines 6 months ahead of flu season so that they can be manufactured in time is a process of sophisticated guess-work, which, if it fails , can lower effectiveness from 70-90% to as low as 50% if there has been significant drift. The reason for this unpredictability, and why people must be re-vaccinated every year, is that the vaccine targets one of the virus’ most variable proteins, haemagglutinin (HA) which is found on the virus surface and is responsible for viruses entering their host cells. Conventional vaccines act by stimulating the production of antibodies against these surface proteins, which will reduce binding, and thus infection, and allow recognition of the virus by the immune system. Harnessing only the humoral immune system (that involving antibodies), means that memory over time is fairly poor and only antigens found on the virus’ surface – which are likely to be the most variable ones – can be targeted.
A new approach aims to target internal proteins through triggering T-cell-mediated immunity, which relies on presentation of antigens from any part of the virus (inside or out) by infected cells. The MVA-NP+M1 vaccine, developed at Oxford University and patented by Vaccitech, has been designed to trigger this form of immunity and is now in clinical trials. MVA is a highly attenuated virus that has been found in the past to boost T cell response. NP (nucleoprotein) and M1 (matrix protein 1) are both very important viral components and so are highly conserved between strains, unlike HA, meaning that targeting them might offer the chance to create a universal flu vaccine where mutations would likely do more harm than good to the virus so the likelihood of failure is less. This, if paired with the traditional trivalent inactivated vaccine, would provide far greater protection against seasonal flu and to the ever present but uncertain threat of pandemic flu . This vaccine might provide a first line of defence while pandemic flu vaccines are in development and could work in conjunction with an antibody-stimulating vaccine in order to cover both branches of adaptive immunity and enhance protection.
