By Professor Miguel O’Ryan
Meningitis: a deadly disease
Meningitis, the inflammation of the protective lining around the brain and spinal cord, is a serious condition for young and old and can be fatal. Typically 1 in 10 victims will die in the UK, a process that can take as little as 4 hours in some cases. While vaccines have been developed for most known subtypes of the meningitis-causing bacteria, Neisseria meningitides, group B currently accounts for approximately 90% of all confirmed cases in the UK. The primary cause being that until now no suitable vaccine had existed for serogroup B. However, Chilean researchers at Universidad de Chile have recently conducted an important randomised controlled trial assessing a new vaccine developed to protect against the remaining Neisseria meningitides b bacteria. The study was published in the prestigious medical journal The Lancet showing that the vaccine successfully caused the production of sufficient antibody levels to combat the bacteria. Project leader and Vice President of Research and Development Professor Miguel O’Ryan talked to Chileno about why the work is important.
The importance of this research
“Three bacteria are responsible for the great majority of severe invasive infections in children and healthy adults: Haemófilus influenza b, Streptococcus pneumonia, and Neisseria meningitides. Thanks to worldwide use of vaccines, the first has practically disappeared in most countries sparing thousands of lives and millions of hospitalizations and sequelae. More recently, vaccines against the most common S. pneumonia serotypes have been incorporated in a significant number of countries with a dramatic decrease in severe bacterial infections caused by these serotypes. For both bacteria the vaccine strategy has been to use capsular polysaccharide as the immunogen which has worked very well in conjugation with a protein carrier. For N. meningitidis four main serogroups infect humans, namely A, B, C, W. Vaccines using the capsular polysaccharide strategy are available as sole or combined for groups A, C and W but not for B. The reason is because the B polysaccharide has an almost identical structure to polysaccharide located in the human brain. Thus, the immune system does not recognize as “different” this molecule and does not create a robust immune response. N. meningitides b is thus the only remaining bacterial pathogen of the “big three” for which a vaccine was not available. It is a significant cause of bacterial meningitis and meningococcemia in many countries in Latin America, Europe and North America. Incidence goes from 0.5 up to 5-10 cases per 100.000 population with a lethality rate of 5-10% and sequelae (listening impairment, motor or cranial nerve palsies and others) that can affect an additional 10 to 15% of survivors. Using a new approach, referred to as “reverse vaccinology”, the complete genome of the bacteria was sequenced, all structural proteins were identified, mice were inoculated with these proteins in order to determine which protein induced a robust immune response. Finally, a selection of “immunogenic proteins” located in the bacterial surface and present in a large group of different N. meningitides b subtypes lead to the vaccine of “protein nature” containing 4 main bacterial proteins.
Our study was a clinical evaluation of the vaccine in adolescents in order to determine immunogenicity and safety and to define how many doses would be required in this age group to produce a “protective immune response”. After enrolling over 1500 adolescents, receiving one, or two, or three doses of vaccine we concluded the two doses were highly immunogenic at month 7, better than one dose, and similar to three doses. This study complements the studies done by other colleagues in young infants in which three doses proved to be better than two. The vaccine was moderately reactogenic, mostly at the local level (redness, pain at the vaccine site) albeit quite tolerable in the adolescents.
Thus, this new vaccine proved to be promising in “closing the loop” of the main bacterial pathogens causing severe infections in children and young healthy adults. Some questions remain, especially how long does immunity last, but this will probably have to be answered after vaccine introduction and use in different settings.”
“I am currently Vice President for Research and Development at the University of Chile which takes most of my time. My research is currently focused on another bacteria, Helicobacter pylori, albeit at a more basic level. We are trying to understand the dynamics of infection in young children, and the possible impact of this early persistent infection in disease outcome further in life. Other groups continue with N. meningitides b performing clinical research in combined vaccines (including group B protein with the other groups which are polysaccharide remember, in order to create one vaccine for all groups), studies aimed to determine the duration of immunity (we have an extension study up to one year of age in finishing phase), and new possibly less reactogenic new generation vaccines (at earlier stages).”