A new protein conjugate vaccine for polymicrobial diseases: a case study (POET)

Abstract number: 1732_141

Hausdorff W.P.

Bacterial respiratory tract infections are a leading cause of morbidity and mortality in young children. Effective immunisation strategies against these infections have to contend with both the multiplicity of pathogens and a host of disease syndromes. Streptococcus pneumoniae (pneumococcus), and both encapsulated and non-encapsulated forms of Haemophilus influenzae (Hi), are the leading pathogens. More than 90 serotypes of pneumococci exist, but only 10 serogroups appear to be responsible for 80–85% of invasive pneumococcal disease and pneumococcal otitis media (OM) worldwide, ranging from the relatively rare but clinically severe meningitis, to the more frequent infections of the bloodstream and the lungs, such as pneumonia and finally to the extremely common middle ear infections among young children.

Middle ear infections are often associated with diagnostic uncertainty, frequent use and misuse of antibiotics, and recurrent and persistent disease. Recurrent infections occur in as many as 10% of children <3 years of age. Recurrent and persistence disease can lead to temporary or even permanent hearing loss and surgery (tube placement). In order to address these issues, preventive acute OM (AOM) strategies should include a vaccine with broader pneumococcal serotype coverage as well as protection against additional otopathogens.

This presentation describes a novel vaccine approach in which polysaccharides from the 11 leading streptococcal paediatric serotypes are conjugated to a carrier protein (protein D) derived from Hi. In the Pneumococcal Otitis Media Efficacy Trial (POET), conducted in infants and young children in the Czech and Slovak Republics, this approach resulted in substantial protection against pneumococcal and Hi diseases. In this study, an 11-valent investigational conjugate vaccine was concomitantly administered with diphtheria, tetanus, pertussis (DTP) vaccines. The clinical diagnosis of AOM was confirmed by both a paediatrician and an otorhinolaryngologist, and tympanocentesis was performed on children with confirmed AOM. Vaccine efficacy against any AOM episode caused by vaccine-type pneumococci was 57.6% (95% CI: 41.4–69.3%), and efficacy against AOM caused by nontypeable Hi was 35.3% (1.8–57.5%). Most strikingly, the overall impact of the vaccine in this setting was to reduce all AOM by 33.6% (20.8–44.3%). These results suggest that a vaccine that targets these two major groups of bacterial pathogens would have a significant public health impact.