25 October 2017

Goodbye, pneumonia?

New pneumonia vaccine will prevent the "wildness" of the microbiota

Daria Spasskaya, N+1

Researchers from the University of Buffalo have developed a new type of pneumonia vaccine – unlike other vaccines, it does not create immunity from pneumococci, but prevents the transition of any strains of pneumococci into a dangerous state. The article was published in the journal Science Advances, the press release can be found on the university's website.

Bacteria Streptococcus pneumoniae in many people are a component of the healthy microflora of the upper respiratory tract. However, these same bacteria are the most common cause of pneumonia, cause meningitis, nasopharyngeal and ear infections. Pneumococcal infections are especially dangerous for children, the elderly and people with weakened immune systems. According to WHO, 500 thousand children under the age of five died as a result of infection in 2008. There are vaccines for pneumococcal infection, and WHO strongly recommends their use for people at risk. In Russia, the pneumococcal vaccine is included in the National Calendar of Preventive Vaccinations.

There are more than 90 serotypes (varieties) Streptococcus pneumoniae, however, vaccines cover a maximum of 23 of the most aggressive. Serotypes differ in the composition of polysaccharides on the surface of bacteria. Existing vaccines either contain several types of polysaccharides attached to a protein that increases the immunogenicity of the drug (so-called conjugated vaccines, for example, Prevnar 13, covering 13 serotypes), or simply contain purified polysaccharides (Pneumovax 23, covering 23 serotypes).

Despite the successful prevention of bacterial pneumonia and other infections due to vaccination, the mortality rate from it still remains high. Approximately ten percent of cases of the disease occur in the remaining serotypes of pneumococcus. Scientists are considering various strategies to optimize vaccines in order to expand their protective effect. It is quite difficult to simply include all 90 serotypes in the vaccine – the production of such a vaccine will be very expensive. In addition, the preventive destruction of bacteria that are part of the normal human microflora is undesirable – strains to which the body is already "used" are quickly replaced by pathogenic microflora.

Researchers from the University of Buffalo comprehensively approached the issue of improving the vaccine. Instead of "sewing" polysaccharides to the protein, the authors proposed to pack them into liposomes – bubbles surrounded by a lipid membrane (this technology was called LEPS – liposomal encapsulation of polysaccharides). A protein component was added to the composition of the liposome membrane. This strategy makes it easy to add new serotypes to the vaccine while maintaining high immunogenicity.

LEPS1.jpg
Scheme of obtaining conjugated vaccine and liposomal
Drawings from an article in Science Advances.

In their previous work, scientists found that most serotypes Streptococcus pneumoniae (about 70) during the transition from a "peaceful" to a virulent state begins to synthesize certain markers – GlpO and PncO proteins. Developing immunity against these proteins will allow the body to attack bacteria only if they turn into a dangerous form.

LEPS2.jpg

Efficacy of immunization of mice with PCV13 (red), PPSV23 (green), LEPS20/PncO+ vaccines GlpO (blue) against serotypes 19F, 11A, 35C. Serotype 35C is not covered by existing vaccines, so infection leads to increased mortality of animals. However, the LEPS20/PncO+ vaccine GlpO provides protection against all three serotypes. The control (saline solution) is indicated in black.

The authors also added GlpO and PncO proteins to the liposome membrane. The resulting LEPS20/PncO+ vaccine GlpO immunized mice and rabbits and confirmed the production of antibodies. When compared with existing LEPS20/PncO+ vaccines GlpO showed the best protective effect even against serotypes that were not included in its polysaccharide component, with artificial infection of animals.

The researchers calculated that the introduction of a new vaccine into the preventive calendar that prevents the transition of pneumococci to a virulent state by 2030 will reduce the number of pneumococcal infections among children and the elderly by five times.

LEPS3.jpg

The incidence of pneumococcal infections among children. After the introduction of PCV7 (red) and PCV13 (orange) vaccines, the number of cases of infection with serotypes included in the vaccines decreased by 100 times, but the frequency of infections caused by the remaining serotypes remains at a constant level. Introduction to the prevention of LEPS20/PncO+ vaccine GlpO should lower this level.

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