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TB Booster Better Off Alone

Sat, 25th Jun 2011

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A new study has shown that a breakthrough vaccine against tuberculosis may be more effective when given alone, rather than alongside other vaccines. 

A study by Martin Ota and colleagues on 4-month old West African infants, found that a next-generation TB vaccine, known rather unspectacularly as MVA85A, is significantly less effective when given alongside other, conventional vaccines.Flu Vaccine administration

TB is a major health problem worldwide, and the existing vaccine, Bacille Calmette-Guérin, or BCG, named after its inventors, is not entirely effective. The rise of drug-resistant TB strains is making the need for a top-up vaccine in addition to the BCG ever more pressing.

This was the aim of a team at Oxford University that created the MVA85A vaccine. They started with a strain of vaccinia virus – that’s the poxvirus which was used as a vaccine to immunize against, and ultimately eradicate, smallpox. The so-called ‘Modified Vaccinia virus Ankara’, or MVA, was then manipulated genetically to express a protein found on Mycobacterium tubercolosis, called 85A. The immune response against 85A protects against tuberculosis, as it primes the immune system to target the TB-causing bacteria.

The modified vaccinia virus is important because it biases the immune system towards generating killer cells that attack pathogens directly, rather than using soluble molecules like antibodies. This so-called ‘cell-mediated’ immunity is essential to fighting off TB effectively.

Martin Ota and colleagues at Oxford had already demonstrated that MVA85A is safe and effective at boosting TB immunity in animal models, and preliminary studies on people in Africa and the UK are showing promise. In this latest study, the authors randomly divided a sample of 4-month old children from the Sukuta Health Centre in Gambia into three groups: one group received the standard selection of vaccines called the ‘Extended Program of Immunization’, or EPI, recommended by the World Health Organization. This includes vaccines against Hepatitis B, diphtheria, tetanus and others. The second group received the EPI plus the new TB vaccine – MVA85A. And the last group received just the MVA85A alone, without the other vaccines.

The scientists then measured the amount of Interferon-gamma (IFN-γ) produced by the participants of the study, at 4 and 20 weeks post vaccination. IFN-γ is a signalling molecule that pushes the immune system towards cell-mediated, rather than antibody-mediated, immunity (and remember that was important for combating TB). They found that MVA85A was significantly better at inducing IFN-γ, and so promoting cell-mediated immunity, when given alone, rather than when given alongside the other vaccines.

This may be because the other vaccines induce antibody responses in the immune system, rather than the killer cell-mediated immunity, and the two immunological strategies are known to inhibit one-another.

So, the study shows firstly that this new TB vaccine is safe, and could work at boosting cell-mediated immunity against TB, and secondly that public health experts may have to re-evaluate how multiple vaccines are given together to children in the developing world.

And that work was published this week in the journal, Science Translational Medicine.

Ben: -   I assume the reason that they've given lots of vaccines at once is because they're exposed to a wide range of different potential infection so actually, delaying something that could introduce its own risk.

Will: -   Yeah and one of the main reasons why they're given at once is purely practical, just because it’s very difficult to get people from remote rural communities and many of these countries in the developing world into the clinics to receive the vaccines and so, it would be much better if you could do it all in one go.

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Most interesting. 

Is this one of the first times that a live viral vaccine has been genetically modified to fight a bacterial disease?

If effective, I could see it opening new avenues of research, perhaps into Malaria vaccines, or AIDS vaccines.

Does the effectiveness of this TB vaccine depend on whether or not a person has previously received the smallpox vaccine?  Since most smallpox vaccines have been stopped years ago, perhaps those individuals aren't a big problem now, but it could limit using the same virus vector to deliver multiple different vaccines in the future.

As noted in the interview.



It is possible to have very complex vaccine regimens in the USA and Europe, but it is far more difficult to give children in the 3rd world repeated doses of vaccine, which is one of the reasons why they often don't use 3 doses of IPV followed by one dose of OPV even though the more complex regimen is safer.

Perhaps another avenue of research would be to modify something like the varicella virus/vaccine to generate immunity for varicella PLUS something else. CliffordK, Mon, 27th Jun 2011

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