Caucasian connection could help find anthrax vaccine

Bacillus anthracis bacteria Gram stain
Most vaccines are developed by commercial companies to make money. Although anthrax is a terrible disease that can be tragic for those who contract it, it’s a relatively rare disease and, as a consequence, there is no real market for a vaccine. Professor Les Baillie
Researchers from the United Kingdom, the Republic of Georgia, Turkey and the United States are combining their skills and resources in a new project aimed at finding a vaccine for anthrax. This multinational research project is funded as part of NATO’s Science for Peace and Security Programme to look at ways of tackling the bacteria that has been used in the past as a lethal bioweapon.

Members of the team are hopeful that the technology and expertise shared with collaborators in the Caucasus will contribute to the development of stronger scientific infrastructure in Georgia, and provide a basis for tackling other pressing infectious disease issues there in the long run.

Leader of the study Professor Les Baillie, from the School of Pharmacy and Pharmaceutical Sciences at Cardiff University, spoke to ScienceOmega.com about the nature of anthrax infection and the difficulties presented by the attempt to find a more effective human vaccine...

How does anthrax infect and affect the human body?
The commonest route of infection by anthrax is from infected animal products. It primarily affects cows, but goats and various other domestic animals can also be infected. They contract the disease and die, but the spores can linger on animals furs and meat and can be passed on to people that handle them. These spores are very resistant and long-living. Anthrax can survive for decades, if not hundreds of years, posing a continual risk.

There are other forms of infection, too. In the United Kingdom there is currently an outbreak caused by the contamination of heroin with anthrax. Last year there were a number of fatalities in this country and, indeed, another outbreak has just begun with a case in Blackpool. Somehow the anthrax spores have got into the heroin and users then inject them directly into their bloodstream.

The majority of cases are skin infections, known as cutaneous anthrax. You get horrible lesions which respond to antibiotics and normally get better. The other form is gastrointestinal anthrax, which is contracted by eating contaminated meat. You might wonder why people would eat that meat, but in certain parts of the world protein is in very short supply and people are loath to throw away animals that have died.

The final form, which is of particular concern to the defence community, is inhalational anthrax, where you inhale an aerosol. This would be in the form of a sort of mist of spores, invisible and tasting of nothing. Once the spores are inhaled, however, and they go on to cause a systemic disease that can be fatal in two to three days.

How effective are current methods of detecting Bacillus anthracis, in the environment and in cases of infection?
As a caveat, there may be methods which exist that I’m not aware of. I am aware of the American approach, which is to have a system of sensors located in their major cities running 24/7 and ‘sniffing’ the air for the presence of Bacillus anthracis; it’s called the BioWatch program. It’s a very costly and time-consuming process, and I’m not aware that any other country has anything similar.

There are diagnostic tests, but you have to have an index of suspicion with many of them. The problem is that B. anthracis infection presents in ways very similar to a number of other diseases; it’s very non-specific in the early stages. Unless you had a differential diagnosis you wouldn’t necessarily think ‘anthrax’. Conversely, if 10,000 people turned up at your surgery exhibiting those symptoms you might have a clue that something was amiss.

What are the main challenges in developing an effective vaccine for anthrax?
There are two main challenges. Firstly, the number of cases. Most vaccines are developed by commercial companies to make money. Although anthrax is a terrible disease that can be tragic for those who contract it, it’s a relatively rare disease and, as a consequence, there is no real market for a vaccine. The pounds and dollars required to make such a thing are hard to come by. It’s estimated that a vaccine would cost around $800 million to develop, and so the economic driver for doing so is not very high.

There are existing anthrax vaccines available in the United Kingdom and the United States. These have been around for decades, although there have been some concerns regarding transient side effects.

The vaccine requires multiple dosing which suggests it is not particularly immunogenic, but the problem with anthrax vaccines is that we have no real way of testing whether they work in humans. We can do studies on animals, but at the end of the day our physiology is not the same. That’s another challenge for making vaccines – finding parts of the world where the disease is a real issue so that we can demonstrate that any vaccine we develop works. That is when you come into the realm of Phase 3 clinical trials.

Why is international collaboration so essential to the success of this project?
Fortunately for us, anthrax is a rarity in the West, outside heroin and other very specific instances. That is not the case in other parts of the world, however. In Central Asia and parts of Africa there are still significant numbers of human cases. Many of these countries still have agrarian societies and as a consequence people are exposed to the naturally-occurring bacteria.

We are collaborating with colleagues in the Republic of Georgia, in the Caucasus, and Turkey, which borders Georgia. That part of the world does see human and animal cases of anthrax, which – it’s sad to say – is useful for us, because it means we can look at patient immune responses and possibly have the chance to carry out trials in the future.

What are the first steps for the work the project is going to carry out?
Vaccine targets have been described for anthrax – they do exist. The question is whether they are sufficient in themselves to give good protection. We are interested, therefore, in identifying the key reasons for the known vaccine targets, using immunology, but also in investigating other targets which could be added to the mix, as it were.

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