Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B

Kuipers, Kirsten; Diavatopoulos, Dimitri A.; Opzeeland, Fred van; Simonetti, Elles; Kieboom, Corné van den; Kerstholt, Mariska; Borczyk, Małgorzata; IngenSchenau, D. van; Brandsma, Eelke; Netea, Mihai G.; Jonge, Marien I. de

doi:10.1093/infdis/jiw160

Cited by 15 publications

(12 citation statements)

References 37 publications

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“…Of note, Xue et al also demonstrated that the mucosal group immunized with an adjuvant elicited a greater response than the group without adjuvant. Our finding of rapid clearance of GBS from both the control and GBS-immunized mice via the intramuscular route demonstrate a potential role for systemic adjuvant in GBS colonization clearance, a non-specific effect shown by other groups [49]. …”

Section: Discussionsupporting

confidence: 56%

Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization

Baker

Lewis

Byland

et al. 2017

Vaccine

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Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants, and colonization of the maternal genital tract is the primary risk factor for newborn infection. Despite the importance of mucosal colonization in GBS pathogenesis, relevant host and bacterial factors are incompletely understood. We investigated the role of humoral immunity in clearance of vaginal colonization in vivo. B-cell-deficient mice or those lacking neonatal Fc-receptor, a mediator of IgG transport to the vaginal mucosa, exhibit prolonged GBS vaginal colonization compared to wild type animals. Intranasal but not intramuscular immunization induced systemic and mucosal immune responses and decreased GBS colonization duration without altering initial colonization density. Vaccine-induced clearance of GBS was serotype-specific, suggesting a role for anti-capsule antibodies in protection. Our results support a role for humoral immunity in GBS eradication from the female genital tract and suggest that mucosal vaccination may prime colonization clearance.

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Section: Discussionsupporting

confidence: 56%

Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization

Baker

Lewis

Byland

et al. 2017

Vaccine

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“…This non-specific immunity against pneumococcal colonization in mice was recently associated with the activation of local innate response, involving activation of the caspase-1/11 inflammasome, mucosal T cells and macrophages [35]. An increase in IL-1β and macrophages was observed in the nasal tissue of animals inoculated with CTB.…”

Section: Discussionmentioning

confidence: 99%

Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae

et al. 2017

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A promising alternative vaccine candidate to reduce the burden of pneumococcal diseases is the protein antigen PspA (Pneumococcal surface protein A). Since concomitant colonization with two or more pneumococcal strains is very common in children, we aimed to determine if immunization with PspA would be able to control co-colonization. We evaluated nasal immunization with recombinant PspA (rPspA) in a model of co-colonization with two strains expressing different PspAs. Mice were immunized intranasally with rPspAs from clades 1 to 4 (rPspA1, rPspA2, rPspA3 or rPspA4) using whole-cell pertussis vaccine (wP) as adjuvant. Mice were then challenged with a mixture of two serotype 6B isolates St491/00 (PspA1) and St472/96 (PspA4). Immunization with rPspA1+wP and rPspA4+wP reduced colonization with both strains and the mixture of rPspA1+rPspA4+wP induced greater reduction than a single antigen. Immunization rPspA1+rPspA4+wP also reduced colonization when challenge experiments were performed with a mixture of isolates of serotypes 6B (PspA3) and 23F (PspA2). Furthermore, none of the tested formulations led to a pronounced increase in colonization of one isolate over the other, showing that the vaccine strategy would not favor replacement. Interestingly, the adjuvant wP by itself already led to some reduction in pneumococcal colonization, indicating the induction of non-specific immune responses. Anti-rPspA IgG was observed in serum, nasal wash (NW) and bronchoalveolar lavage fluid (BALF) samples, whereas animals inoculated with formulations containing the adjuvant wP (with or without rPspA) showed higher levels of IL-6 and KC in NW and increase in tissue macrophages, B cells and CD4+T cells in BALF.

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“…S4B), suggesting that IL-17A may contribute to the nonspecific decrease in pneumococcal loads. Mucosal adjuvants such as cholera toxin subunit B (CTB) and cholera toxin (CT) were also described to reduce pneumococcal colonization in a nonspecific manner, although the underlying mechanisms may differ (23,24). The nonspecific increase in the IL-17A concentration might be derived from (25,26).…”

Section: Figmentioning

confidence: 99%

Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen

et al. 2017

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Serotype-specific protection against Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from Salmonella enterica serovar Typhimurium displaying the variable N terminus of PspA (␣1␣2) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single ␣1␣2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.KEYWORDS intranasal vaccination, protein antigens, Streptococcus pneumoniae, PspA, colonization, Th17, broad protection, Salmonella outer membrane vesicle (OMV), antigen surface display, autotransporter Hbp R espiratory bacterial infections remain a major cause of severe morbidity and mortality worldwide in both infants and adults (1, 2). Vaccination is considered one of the most cost-effective strategies to reduce the global burden of infectious diseases, the associated health care costs, and the risk of emerging antibiotic-resistant strains (3). Vaccination against Streptococcus pneumoniae is implemented in different parts of the world. However, about 1 million children still die of pneumococcal disease every year (1, 2). Pneumococcal polysaccharide conjugate vaccines are designed based on epidemiological data from the Western world. These vaccines protect against serotypes that are the most prevalent and most frequently associated with severe invasive disease. They induce serotype-specific protection against 13 of the 97 identified serotypes that are circulating worldwide (4). This is an important limitation, and during the last decade, nonvaccine variants of S. pneumoniae that cause severe invasive disease have Citation Kuipers K, Jong WSP, van der Gaast-de Jongh CE, Houben D, van Opzeeland F, Simonetti E, van Selm S, de Groot R, Koenders MI, Azarian T, Pupo E, van der Ley P, Langereis JD, Zomer A, Luirink J, de Jonge MI. 2017. Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen. Infect Immun 85:e00281-17.

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Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B

Cited by 15 publications

References 37 publications

Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization

Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization

Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae

Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen

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