by Dr. Tim Bull
This paper, entitled Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine, describes the initial safety studies in humans of a vaccine that is designed to stimulate immune recognition of specific components of the MAP bacterium called gsd, ahpC, mpa and p12. It does this by using a harmless virus, originally found in chimpanzees, to deliver MAP components in a manner that activates and educates powerful cells in the body’s immune repertoire so that they recognize which of their own cells are infected with MAP. Once primed, these immune cells can home in and either kill infected cells and the MAP organisms inside them or stimulate mechanisms in the infected cells so that they are able to eliminate these persistent invading organisms on their own.
Preliminary testing of this vaccine in animals infected with MAP showed good promise but used a human form of the harmless virus to make the delivery. However recent trials of an HIV vaccine that also used this virus as a delivery system, showed that some patients already had antibodies against the delivery virus and these reduced the overall vaccine’s efficiency. By using a delivery virus from a chimpanzee, this study aimed to avoid these potential issues, as humans are very unlikely to have encountered them previously and made antibodies.
The study was a Phase I type which involved monitoring the giving of a single dose of vaccine to three groups of three healthy volunteers, with each group getting a different amount of vaccine (low intermediate, high). The study observed a few mild short term reactivities to vaccination but importantly, no adverse serious events in any of the volunteer subjects. This is very encouraging and would mean further studies could be justified.
Tests were included to see if the vaccine had stimulated the expected MAP specific immune responses. These included looking for immune reactivity overall and also to each of the four specific MAP components. It was found that the group of three subjects given the intermediate vaccine dose responded the best, but this was only moderate and peaked at 28 days. The study was not designed to investigate if this responsiveness would be sufficient to address a MAP infected human and no attempt was made to look for live MAP bacteria in these subjects, although at least one subject had reactivity to MAP antigens prior to being vaccinated.
The study did not find specific chimpanzee virus antibodies against the vaccine before dosing but did see them being made after. There was evidence however that some subjects had cross reacting antibodies against a related chimpanzee virus that had been given to some subjects in a previous trial (against influenza) and that this may have reduced efficacy in some vaccinations. Importantly, there was no evidence of cross reactivity from human types of the delivery virus. This is again encouraging suggesting this type of vaccine is unlikely to be diminished by previous exposure to common human viral infections.
In summary this approach to vaccination was safe in humans and had the capacity to stimulate a modest and possibly transient immune response against MAP. Further studies to test the possibility of adding a second boosting dose using either the same vaccine or one that boost delivers the same MAP components via yet another type of delivery vector is warranted.
Dr. Tim Bull is a Reader in Infectious Diseases at St George’s, University of London. He is an internationally recognized expert in mycobacterial diseases and has over 20 years experience in working with culturing mycobacteria. Prior to gaining his PhD at Imperial College in 1995, Dr. Bull worked in a number of medical microbiology and virology laboratories around London including The Royal Free London NHS Foundation Trust, Chelsea and Westminster, Charing Cross, and Hammersmith Hospitals as a biomedical scientist. He has a BSc in Biological Sciences and uniquely has two Special Fellowships with the Institute of Medical Laboratory Sciences (Medical Microbiology and Virology).
Dr. Bull was instrumental in the initial design and development of the original vaccine and testing the efficacy of a prime-boost version in animals with MAP infection. He is also one of the researchers participating in Human Para’s inaugural Crohn’s/MAP Testing Study.