As I reflect on the more than 30 years I have worked in the vaccine field, I think one of the most exciting advancements has been the progress made in developing vaccines to protect against meningococcal meningitis, a devastating bacteria-borne disease that can occur suddenly and lead to death within 24 to 48 hours of the first symptoms. And, for those who survive, it can cause serious, life-long disabilities, including brain damage, hearing loss, and limb amputation.
This year marks the 125th anniversary of Anton Weichselbaum’s discovery of the causative bacterium Neisseria meningitidis. In the years since his seminal discovery, the scientific community has made great strides in learning about this disease, how to treat it, and most importantly, how to prevent it.
In the early 1990s, when I was a part of Chiron Corporation (now Novartis), I helped develop the first conjugate vaccine against meningococcus A and C. The promising results were the basis for a collaboration with the public health authorities of the United Kingdom to develop and test meningococcal C conjugate vaccines. In 2000, Chiron, Baxter, and Wyeth (now Pfizer) provided the vaccines for a country-wide immunization campaign that led to the near-elimination of meningococcus C cases in the U.K. after just 1 year. Then, in 2004, in partnership with the New Zealand Ministry of Health, a vaccination campaign was initiated against meningococcal serogroup B (MenB) using a vaccine specifically targeting the strain of meningococcus B causing the epidemic. Again, within a year, we had eliminated the spread of MenB in New Zealand.
Based on these examples, we now know eliminating meningococcal disease is possible through vaccination, but we face some challenges. While there are vaccines that provide broad protection against four of the major meningococcal serogroups (A, C, W-135, and Y), these strains cause only about 50 percent of meningococcal disease. The remaining 50 percent is caused by MenB, for which no broad-spectrum vaccine is available; the vaccine we developed in New Zealand was only effective against one strain circulating in the country at the time.
The capsular polysaccharide of MenB cannot be used to create a universal vaccine because it has a chemical composition identical to a polysaccharide present in our body (polysialic acid), and is therefore not recognized as foreign by our immune system. MenB is the final frontier of meningococcal meningitis prevention.
To overcome this hurdle, Novartis researchers are using reverse vaccinology to develop our MenB candidate vaccine, Bexsero. We began exploring this technology in the late 1990s, after Craig Venter sequenced the first bacterial genome. We then began working with Venter to develop the process, which involves decoding the genetic makeup of a bacterium to predict the antigens that are likely to be on the surface of the bacteria. This approach provides instant access to entire antigen repertoire and allows fast identification even of those antigens that would be difficult or impossible by the conventional methods involving the time-consuming and expensive processes of growing the bacteria in culture and purifying their components. In the case of MenB, however, one of the antigens discovered by us was also identified by conventional approaches by scientists at Pfizer, and they are also using it to develop a MenB vaccine.
Our past experience has shown that we are able to eradicate meningococcal disease in isolated countries and regions. Our MenB candidate vaccine was submitted for regulatory approval in Europe in December 2010, and Pfizer’s vaccine candidate continues to be vetted for safety and efficacy. I remain confident that in the future, we can eradicate meningococcal disease, including the elusive MenB, on a global level.
Rino Rappuoli is the global head of research at Novartis Vaccines and Diagnostics.