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Thursday, 28 April 2016

57 Varieties

Global Traveller: Chlamydia infection varies by region

A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance.

Vaccines come in various flavours. Some are purified from the toxic by-products of bacteria (tetanus), some are made of sugar (pneumonia), some are made of protein (HepB), some are made of sugar mixed with protein (meningitis), some are live but weakened (BCG) and some are dead (flu). There are various reasons for making them from different things, including cost, formulation and the part of the bug we are trying to target with the vaccine.

Form follows function

The make up of vaccine has a direct effect on the type of immune response it induces. Sometimes, vaccines can induce an immune response, but the immune response they induce is not able to kill the bug. For example there are 2 whooping cough (Bordatella pertussis) vaccines available: whole cell or wP (made up of whole bacteria that have been killed) and acellular aP (made up of 3 or 4 individual proteins from pertussis). Most higher income countries switched to aP about 20 years ago because the vaccine is less reactogenic – wP can lead to a high temperature and a sore arm. However we are seeing a resurgence of whooping cough in the countries that switched vaccines. Dissecting the response to the 2 different vaccines has shown that the wP vaccine leads to a different type of immune response to aP, switching the way the T cells (a white blood cell) react to the bug (from Th1 to Th2 if you need to know). This switch in response, is associated with the reduced effectiveness of the vaccine. NB – aP still works, it is still safe, you should still get it for your children and when pregnant, it just doesn’t work as long as wP.

Number 1 bacteria

Chlamydia trachomatis is the most common STI caused by a bacteria – over 141 million infections occurred in 2013: those of you paying attention will remember this also causes eye disease. It is mostly asymptomatic (you can’t tell if you’ve got it), but in about 5% of cases it can cause a condition called pelvic inflammatory disease, which if not treated can level to infertility. Treating Chlamydia is expensive – over US$3 billion are spent in the US alone each year. Based on the burden of disease and the cost of treatment, there is a strong case to make a vaccine against chlamydia. However, this has proved difficult, this is in part because we don’t know what type of immune response would be best to stop it. We therefore set out to explore this, exploiting the fact that different vaccine types lead to different immune responses. Alex (the lead author) made 4 different vaccines based on the same protein derived from chlamydia (the major outer membrane protein or MOMP). These were a DNA vaccine, an Adenovirus, a Modified vaccinia Ankara and a Protein, conveniently leading to the acronym DAMP.

DAMP-proof course

In our recently published study we investigated the effect of changing the types of vaccine on the immune response. We could make a response that was just antibody (PPP) or just T cells (DDD) or a mix of the two (DAMP.) We then measured whether these different types of response altered the outcome of infection. Only the DAMP (which gave a mixed immune response) regime reduced the number of chlamydia bacteria after infection. This protection disappeared when the T cells were blocked, suggesting they were required. Based on these studies, we believe a Chlamydia vaccine needs to induce a mixed response, with both T cells and antibody. This work has informed a clinical trial in healthy volunteers to test the ideas further. It is yet another example of work funded by the EU, which if we left, would not be possible.


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