Intranasal vaccination with γ-irradiated <i>Streptococcus pneumoniae</i> whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses

Babb, Rachelle; Chen, Austen; Hirst, Timothy R.; Kara, Elodie; McColl, Shaun R.; Ogunniyi, Abiodun D.; Paton, James C.; Alsharifi, Mohammed

doi:10.1042/cs20150699

Cited by 41 publications

(49 citation statements)

References 62 publications

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“…We did not study a role of cellular immune responses in preventing Spn infection. Wilson, et al have shown that both humoral and cellular immune responses are required to protect against Spn infection [30], Antibody-independent immunity such as CD4-mediated and IL-17-mediated T-cell response and TLR-mediated innate responses may play critical roles in protection against Spn infection [28, 2, 12, 30, 11, 8, 15]. …”

Section: Discussionmentioning

confidence: 99%

Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children

Casey

Almudevar

et al. 2017

Clinical Microbiology and Infection

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Objectives We previously found that nasopharyngeal (NP) colonization by Streptococcus pneumoniae (Spn) elicits mucosal antibody responses to three protein vaccine candidates: pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin (PlyD1). Here we sought to determine if mucosal antibody levels to the proteins correlated with protection from acute otitis media (AOM) and NP colonization. Methods 228 NP samples were prospectively collected from 100 healthy infants at 6–24 months of age. Whenever children were diagnosed with AOM, middle ear fluids were collected to confirm the diagnosis by microbiologic culture. NP mucosal IgG and IgA were quantified by ELISA. Results Higher NP mucosal antibody levels to Spn proteins correlated with significantly decreased likelihood of developing AOM caused by Spn during 3 to 12 months of subsequent prospective monitoring. Specifically, children who did not experience AOM (n=111 samples) caused by Spn had 2-5-fold higher mucosal IgG levels to PcpA (all p values <0.01), 6-8-fold higher IgA to PhtD (all p values <0.05); 2-3-folder higher IgA to PcpA (all p values <0.05), and 2-3-fold higher IgA to PlyD1 (p=0.08, 0.03 and 0.08) compared with children who did experience AOM (n=18 samples). No association between mucosal antibody levels to the three proteins and NP colonization with Spn was found. Conclusion Higher NP mucosal IgG levels to PcpA, and IgA to PhtD, PcpA and PlyD1 correlate with reduced risk of development of Spn AOM infection but not with reduced risk of NP colonization in young children.

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Section: Discussionmentioning

confidence: 99%

Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children

Casey

Almudevar

et al. 2017

Clinical Microbiology and Infection

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“…For this assay, splenocytes from 3 mice from LTB, Sp GlpO, Sp GlpO adjunct or MalX-immunized group were harvested and concentrations of IFN-γ, interleukin (IL)-6, IL-10 and IL-17A were measured in supernatants of antigen-stimulated splenocytes at 72 h by sandwich ELISA, using mouse ELISA Ready-SET-Go kits (eBioscience; Cat Nos 88-7314-88, 88-7064-88, 88-7104-88, 88-7371-88, respectively), essentially as described recently (Babb et al, 2016). Concanavalin A was used as a control, and concentrations of cytokines in supernatants were determined relative to the standard curve generated using cytokine standards provided by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates

et al. 2017

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Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lacto/neolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease.

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“…The Th17 response deserves a special note because it could provide a serotype-independent defence mechanism involving B cells and innate interleukin (IL)-17 [61]. Furthermore, IL-17 producing CD4 T cells specific for one serotype were effectively de-colonizing another serotype not expressing the specific antigen [62,63].…”

Section: Protein Conjugate Vaccinesmentioning

confidence: 99%

From Immunologically Archaic to Neoteric Glycovaccines

Cavallari

Libero

2017

Vaccines

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Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection.

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Intranasal vaccination with γ-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses

Cited by 41 publications

References 62 publications

Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children

Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children

The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates

From Immunologically Archaic to Neoteric Glycovaccines

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