Potential role for mucosally active vaccines against pneumococcal pneumonia

Jambo, Kondwani; Sepako, Enoch; Heyderman, Robert S.; Gordon, Stephen B.

doi:10.1016/j.tim.2009.12.001

Cited by 35 publications

(33 citation statements)

References 75 publications

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“…Together, these results support the use of a proteinbased mucosal vaccine to induce mucosal (in the upper and lower airways) as well as systemic responses. By enhancing immunity in both sites, mucosally active vaccines could increase protection against invasive disease as well as pneumonia (39) and carriage.…”

Section: Discussionmentioning

confidence: 99%

Controlled Human Infection and Rechallenge with Streptococcus pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults

Ferreira

Neill

Bangert

et al. 2013

Am J Respir Crit Care Med

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Rationale: The immunological and protective role of pneumococcal carriage in healthy adults is not known, but high rates of disease and death in the elderly are associated with low carriage prevalence. Objectives: We employed an experimental human pneumococcal carriage model to investigate the immunizing effect of a single carriage episode. Methods: Seventy healthy adults were challenged, and of those with carriage, 10 were rechallenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of the first carriage episode. Serum and nasal wash antibody responses were measured before and after each challenge. Measurements and Main Results: A total of 29 subjects were experimentally colonized. No subjects were colonized by experimental rechallenge, demonstrating the protective effect of initial carriage against subsequent infection. Carriage increased both mucosal and serum IgG levels to pneumococcal proteins and polysaccharide, resulting in a fourfold increase in opsonophagocytic activity. Importantly, passive transfer of postcarriage sera from colonized subjects conferred 70% protection against lethal challenge by a heterologous strain in a murine model of invasive pneumococcal pneumonia. These levels were significantly higher than the protection conferred by either precarriage sera (30%) or saline (10%). Conclusions: Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against recolonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies may be important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.

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Section: Discussionmentioning

confidence: 99%

Controlled Human Infection and Rechallenge with Streptococcus pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults

Ferreira

Neill

Bangert

et al. 2013

Am J Respir Crit Care Med

Self Cite

169

250

View full text Add to dashboard Cite

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“…Pneumococcal diseases are classified into non-invasive pneumococcal diseases (otitis media, sinusitis, non-bacteremic pneumonia) or invasive pneumococcal diseases (IPD) (septicemia, meningitis, pneumonia) (Jambo et al, 2010). S. pneumoniae is the leading cause of bacterial pneumonia worldwide amongst the immuno compromised, the elderly, children under the age of 5, and adults in the developed world which is likely to increase with an aging population (Wardlaw et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Kunda

Alfagih

Miyaji

et al. 2015

International Journal of Pharmaceutics

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Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immune compromised, the very young and the old, and remains one of the leading causes of death.A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in L-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ~150 nm and achieved ~ 20 µg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31±1.32% and MMAD of 1.70±0.03 μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA.

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“…This event is important because a predominance of IFN-γ or IL-4 can direct the immune response towards either a cellular or a humoral response, respectively [23]. Moreover, CD4+ helper T cells can influence effector and memory CD8+ T cell development [20].…”

Section: Discussionmentioning

confidence: 99%

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

Palacios-Martínez¹,

González-Torres²,

Rodríguez-Cruz³

et al. 2012

OJI

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Infections in infants and children under five years of age are a public health in México and are one of the major causes of death. Methods In this study, lymphocyte immunophenotyping for CD3+ (T-cells), CD3+CD4+, CD3+CD8+, CD3+CD19+, CD3+CD16/56+, CD45RA+, CD45RO+, CD62L− and CD28− were determined in the whole blood of gastrointestinal and respiratory bacterial infected children, using a fourcolor flow cytometry technique. Results: Our data showed that the percentages and the absolute numbers of monocytes and granulocytes are increased in infected children, when compared to the control group. Similarly, we observed increases in the percentages of B lymphocytes, CD8+ cells, memory T cells (CD4+CD45RO+ and CD8+CD45RO+) and effector lymphocytes (CD4+CD62L− and CD8+CD28−) in infected children compared with the control group. In contrast, naive T cells were decreased in the bacterial infected children relative to the control group. Additionally, we used ELISA assays to identify the pathogen agent in gastrointestinal and respiratory infection.

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Potential role for mucosally active vaccines against pneumococcal pneumonia

Cited by 35 publications

References 75 publications

Controlled Human Infection and Rechallenge with Streptococcus pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults

Controlled Human Infection and Rechallenge with Streptococcus pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

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