Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

Xu, Qing; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina M.; Pichichero, Michael E.

doi:10.1016/j.vaccine.2015.01.014

Cited by 17 publications

(21 citation statements)

References 47 publications

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“…Other conserved Sp proteins, such as pneumococcal surface antigen A (PsaA), pneumolysin, pneumolysoid PdT, and histidine triad proteins have been used with potent adjuvants as subunit vaccines that protect mice against pneumonia. 24, 26, 27, 29, 33 Although these studies have not directly tested the role of memory Th17 cells in protection against pneumonia, these findings together with our results support the notion that Th17-inducing conserved Sp protein antigens might be vaccine candidates capable of conferring broad protection by inducing strong memory Th17 responses in the lungs.…”

Section: Resultssupporting

confidence: 68%

Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection

et al. 2017

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Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of current pneumonia cases result from infection by serotype strains not included in the vaccine. In this study, we asked if cross-protection against lung infection by heterologous strains can be induced and investigated the underlying immune mechanism. We found that immune mice recovered from a prior infection were protected against heterologous Sp strains in the pneumonia challenge model, as evident by accelerated bacterial clearance, reduced pathology and apoptosis of lung epithelial cells. Sp infection in the lung induced strong Th17 responses at the lung mucosal site. Transfer of CD4+ T cells from immune mice provided heterologous protection against pneumonia, and this protection was abrogated by IL-17A blockade. Transfer of memory CD4+ T cells from IL-17A knockout mice failed to provide protection. These results indicate that memory Th17 cells played a key role in providing protection against pneumonia in a serotype independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells.

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Section: Resultssupporting

confidence: 68%

Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection

et al. 2017

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“…9 We have also shown that vaccination with monovalent and trivalent vaccines containing PhtD, PcpA or PlyD1 confer protection against pneumonia and sepsis in a mouse model. [17][18][19][20] Our work has also demonstrated a correlate of natural exposure-induced higher antibody levels to PhtD, PcpA and PlyD1 with protection against Spn-caused AOM in young children. 21,22 Sufficient promise for the potential of a trivalent PhtD, PcpA, and PlyD1 vaccine has emerged such that one is in human clinical trials for the prevention of pneumonia.…”

Section: Introductionsupporting

confidence: 57%

Modeling specific antibody responses to natural immunization to predict a correlate of protection against infection before commencing a clinical vaccine trial

Almudevar

Pichichero

2017

Human Vaccines & Immunotherapeutics

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“…For example, recombinant Bacillus Calmette-Guerin (BCG) vaccine can decrease the infiltration of neutrophils within airways and reduce the viral loads in BALF in mice infected with respiratory syncytial virus (RSV) showing a potential to prevent pneumonia [157]. Trivalent pneumococcal protein recombinant vaccine vaccination results in a reduction in SP-induced lethality, enhanced early clearance of SP in lungs due to more rapid and thorough phagocytosis of SP by neutrophils, and correspondingly, a reduction in lung inflammation and tissue damage [158]. In addition, cathelin-related antimicrobial peptide appears to be protective in models of pneumonia [159].…”

Section: Neutrophils In Infectious Pneumoniamentioning

confidence: 99%

Advanced Role of Neutrophils in Common Respiratory Diseases

Liu

Pang

Wang

et al. 2017

Journal of Immunology Research

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Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD), pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis) in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

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Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

Cited by 17 publications

References 47 publications

Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection

Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection

Modeling specific antibody responses to natural immunization to predict a correlate of protection against infection before commencing a clinical vaccine trial

Advanced Role of Neutrophils in Common Respiratory Diseases

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