A more effective and less expensive pneumonia novel vaccine is on the horizon thanks to new research.
The novel vaccine against pneumonia, developed by researchers at the Butantan Institute (Brazil) and Boston Children’s Hospital, part of the Harvard Medical School (USA), is now being tested in human patients. According to the researchers the innovation is capable of providing protection against all serotypes of the bacterium Streptococcus pneumoniae.
The research was led by Cerqueira Leite and supported by São Paulo Research Foundation – FAPESP. Phase I and II clinical trials were conducted in Africa and co-ordinated in the US by the Harvard team, with support from the Bill & Melinda Gates Foundation, and the Program for Appropriate Technologies in Health (PATH), a Seattle-based non-profit dedicated to developing innovations that save lives and improve health.
Developing the pneumonia vaccine
Luciana Cezar de Cerqueira Leite, a researcher in the Butantan Institute’s Special Vaccine Development Laboratory, said that in this research the team chose a different strategy to activate the immune response. Instead of targeting the polysaccharides present in the bacterial capsule, as currently available vaccines do, they had opted for proteins common to all serotypes of the microorganism.
Leite said: “It took more than ten years of research to arrive at this cellular vaccine. First, we investigated proteins that could be used as targets. The idea of developing a cellular vaccine occurred to us on the way. We designed the production process and changed the adjuvant [an agent used in conjunction with the vaccine antigen to augment the host’s immune response] as well as the administration pathway.
“Initially, we set out to produce an intranasally administered vaccine, but then we realised that the product would be more efficient if it was administered by intramuscular injection.”
In addition to pneumonia, the S. pneumoniae bacterium causes meningitis, otitis and sinusitis, among other diseases.
The serotypes are defined on the basis of the combination of polysaccharides present in the microorganisms’ capsule. In conventional vaccines, this combination determines the antigen to be introduced into the organism to stimulate antibody production. The vaccine developed by the Butantan Institute triggers an immune response regardless of the bacterial serotype.
Leite said: “We cultured the bacterium without its capsule in the lab and used a special technique to kill it without disintegrating it. So, the inactivated bacterium can be administered as a vaccine. We also identified immunogenic proteins that are common to all S. pneumoniae serotypes.
“In the specific case of pneumonia, insisting on the inclusion of new serotypes in conjugate vaccines only leads to increased complexity and higher production costs, making already expensive vaccines even less affordable for developing countries like Brazil.”
The pneumococcal vaccines currently available are effective against between ten and 13 serotypes, when there are 90 types of this bacterium existing in the world. A nonconjugate version covers 23 serotypes but is used mainly to immunise adults, as it is not effective in children.
“The first generation of conjugate vaccines was effective against the seven most prevalent serotypes in Europe and the US [7-valent]. However, because prevalence varied from one region to another, in Brazil it wasn’t able to provide very good coverage, only about 60%,” she said.
As time passed, it became possible to combine more strains, and eventually 10-valent and 13-valent vaccines were produced, “but there’s a problem with this strategy,” Cerqueira Leite said. “When you take specific serotypes out of circulation, other strains [with different serotypes] emerge naturally, and the existing vaccines lose their efficacy. This is known as serotype substitution.”
As well as being more comprehensive than any current pneumonia vaccine, this new cellular vaccine developed is not vulnerable to the problem of serotype substitution.
“We plan to hold another phase II trial in the US. This is the stage where you compare the type of immune response produced in the populations of different countries,” she said.