Tuberculosis (TB), it is the most deadly infectious disease in the world. ± 1.5 million people die every year as a result of TB. The only vaccine currently available is BCG, but this vaccine has serious limitations.
It works best in young children and protection is transient. After ten to fifteen years the vaccine loses efficacy. Young adults and the elderly are therefore no longer protected, may contract TB and and spread the disease. About 25% of the world's population is latently infected with TB. This means those are not sick but, but if their immune system gets compromised (for example people with AIDS or people using immunosuppressive drugs to treat autoimmune diseases) they may get sick. This, together with increasing antibiotic resistance of TB bacteria, means that there is a great need for a better TB vaccine.
Different types of vaccines
BCG is a so-called live vaccine. BCG is already used for over 100 years and is derived from bovine TB bacteria. A new way of vaccine development is to take a known virus (common cold virus - adenovirus) and attenuate it in such a way that it is no longer pathogenic. With recombinant DNA technology a piece of another pathogen (in this case TB) can be inserted into the virus. A potential risk of virus-based vaccines is that, in addition to an immune response against TB (you want that!), also an immune response is generated against the virus (you don't really want that). In that case the vaccine would be seriously less effective after a second administration because the anti-virus response immediately attack and clear the vaccine. To overcome this, the second vaccine should consist of another viral vector carrying the same TB insert. For instance a lame smallpox virus - vaccinia). The idea is to boost the immune response against TB (you want that!) but not to the viral vector since that is new to the immune system.
Different routes of administration
Since TB is a lung infection, it may make more sense to give a vaccine in the lung in order to locally induce the immune response to TB. The standard way of administering vaccines is in the skin or muscle. This way also protects against infection of the respiratory tract (like flu vaccine).
In the current study, we administered two virus-based TB vaccines via different routes. The first vaccination was done with an adapted adenovirus) containing five inserts of TB bacteria. This strategy is also used for the vaccine that is currently used to fight Ebola virus. For the second round of vaccination we used an adapted smallpox virus (vaccinia). Also this vaccine was used before as a vaccine against other diseases. Both vaccines were either given through in lungs or skin. A non-vaccinated group and a group with the only vaccine BCG were included as a control.
We then looked at whether there was a good immune response against the five different TB pieces and whether the animals were protected against a TB infection.
We found that the various strategies investigated in this study did not appear to protect against TB infection. It should be noted that the well-known BCG vaccine also did not protect in this study. This seems to be consistent with the lack of BCG protection often seen in humans. We did see that it matters through which route you administer the vaccine. Although we saw no protection, it was found that slightly less disease occurred when administered via the skin than when administered via the lung.
Publications with "negative" data are also important
It is important that studies that show no effect of new TB vaccines are also published to prevent studies from being repeated. That is why we published this work in the journal NPJ Vaccines.