RESUMEN
Protein bodies (PBs) are particles consisting of insoluble, aggregated proteins with potential as a vaccine formulation. PBs can contain high concentrations of antigen, are stable and relatively resistant to proteases, release antigen slowly and are cost-effective to manufacture. Yet, the capacity of PBs to provoke immune responses and protection in the upper respiratory tract, a major entry route of respiratory pathogens, is largely unknown. In this study, we vaccinated mice intranasally with PBs comprising antigens from Streptococcus pneumoniae and evaluated the level of protection against nasopharyngeal colonization. PBs composed of the α-helical domain of pneumococcal surface protein A (PspAα) provided superior protection against colonization with S. pneumoniae compared to soluble PspAα. Immunization with soluble protein or PBs induced differences in antibody binding to pneumococci as well as a highly distinct antigen-specific nasal cytokine profile upon in vivo stimulation with inactivated S. pneumoniae. Moreover, immunization with PBs composed of conserved putative pneumococcal antigens reduced colonization by S. pneumoniae in mice, both as a single- and as a multi-antigen formulation. In conclusion, PBs represent a vaccine formulation that elicits strong mucosal immune responses and protection. The versatility of this platform offers opportunities for development of next-generation vaccine formulations.
Asunto(s)
Infecciones Neumocócicas , Streptococcus pneumoniae , Administración Intranasal , Animales , Anticuerpos Antibacterianos , Proteínas Bacterianas , Inmunidad Mucosa , Ratones , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , VacunaciónRESUMEN
OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.