If the vaccine developed by a team at Oxford University (UK) passes successfully through all the phases of human testing, this will really be big news. As it is, it is an enormously hopeful development toward the control of human influenza (the flu) and the threat of pandemics.
Fighting flu viruses is like going after computer malware – it’s always changing, always adapting. It seems like the development of vaccine is always one step behind the mutating viruses; and the whole process of playing catch-up is expensive and fraught with potential errors. The researchers at Oxford decided that trying to outguess or outrun the mutations was, if not futile, perhaps not the most creative way of dealing with the problem.
The team led by Dr. Sarah Gilbert at Oxford’s Jenner Institute decided to go after a different target: the proteins that make up the inner core of viruses. To do this they decided against the traditional method used by most vaccines, which is to stimulate the production of antibodies. Instead they set out to stimulate another part of the body’s immune system, the so called “T-cells” (T lymphocytes). The T-cells don’t look for the ever changing virus proteins found of the surface of the virus, which is what antibodies do; T-cells detect core virus proteins, which are common to almost all strains of virus.
The key to the new approach is targeting two proteins that are found inside the flu virus. The two proteins, nucleoprotein (nucleocapsid protein, NP) and matrix protein 1 (M-protein) are about 90 percent identical in all strains of influenza A. They are wrapped around the virus RNA (viruses use RNA instead of DNA for genetic code) and account for a large proportion of the virus material, which makes them relatively easy to identify. The virus needs nucleoprotein to maintain the structure and condition of the RNA, and the matrix protein 1 forms part of the shell around the virus. Both proteins are vital to the survival of the virus and therefore are highly conserved, as geneticist say, meaning they don’t change from generation to generation. This makes them fixed targets.
T-cells are the ‘memory’ of the immune system. Every time the body is infected with a virus, T-cells are produced that carry receptors designed specifically to ‘recognize’ (chemically) that strain of virus. Almost everyone already has T-cells that recognize the M and NP proteins. However, it typically takes too long for the production of new T-cells of that type to ramp up against a new infection. That’s where the vaccine comes in. It is based on a specially prepared version of a common virus called modified vaccinia Ankara or MVA. The two proteins, NP and M, are literally tacked onto the MVA virus. Their presence stimulates production of activated T-cells, mostly of the cytotoxic variety which attack virus infected cells that carry NP and M proteins – which is most of them.
Does it work? Yes, in a limited study. Keep in mind, the vaccine was cleared in the UK for human testing, but the technical aspects have not yet been published under peer review, nor have large scale human trials been conducted. Nevertheless, in a small sample (11 healthy non-vaccinated, 11 healthy and vaccinated) significantly fewer vaccinated people got the flu than those who were not vaccinated. Testing indicated that the vaccinated people had high levels of T-cells activated for the general type A flu virus. It also showed that the MVA virus used in the vaccine is safe when loaded with the virus proteins. (MVA is known to be a very mild virus, even for children and the elderly.)
The next step is a large field trial of several thousand people. The Oxford team will also work on combining their T-cell vaccine with traditional anti-body vaccine to increase the range of effectiveness. While they don’t expect 100 percent effectiveness against all strains of flu virus, this does seem to be the best shot (pun intended) at developing a kind of universal flu vaccine. We’ll know more in a few years.
