Neonatal mucosal immunization with a non-living, non-genetically modified Lactococcus lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection

Ramírez, Karina; Ditamo, Yanina; Rodriguez, Liliana; Picking, Wendy L.; Roosmalen, Maarten L. van; Leenhouts, Kees; Pasetti, Marcela F.

doi:10.1038/mi.2009.131

Cited by 87 publications

(88 citation statements)

References 37 publications

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“…Although high levels of antibody production in neonates can be generated following mucosal vaccination (11,16,59), our studies underscore the great potential of the neonatal intestinal immune system to promote systemic antibodies that may equal or even exceed adult levels in response to infection. To the best of our knowledge, antiLcrV responses have been reported only in vaccinated adult mice (13,18) or after intranasal delivery to neonatal mice with a vector expressing LcrV (60). Here, we demonstrate that LcrV is also immunogenic through the gastrointestinal tract in response to natural infection.…”

Section: Discussionmentioning

confidence: 61%

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

et al. 2010

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Section: Discussionmentioning

confidence: 61%

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

et al. 2010

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“…Serum IgG antibodies to IpaB, IpaD, and dmLT were measured by an enzyme-linked immunosorbent assay (ELISA) (39,40). Briefly, Immulon II ELISA plates (Thermo Scientific, Waltham, MA) were coated with IpaB (0.1 g/ml), IpaD (1 g/ml), or dmLT (1 g/ml) diluted in PBS for 3 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…The frequency of IgG-and IgAsecreting cells was measured by an enzyme-linked immunosorbent spot assay (ELISpot) as previously described (39,40), with modifications. Spleen, bone marrow, and nasal mucosa-associated lymphoid tissue (NALT) were collected on days 39 and 56 after immunization, and singlecell suspensions were prepared.…”

Section: Antibody-secreting Cells (Asc)mentioning

confidence: 99%

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

et al. 2012

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Shigella spp. are food-and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the development of a broadly protective vaccine. All Shigella spp. utilize a type III secretion system (TTSS) to initiate infection. The type III secretion apparatus (TTSA) is the molecular needle and syringe that form the energized conduit between the bacterial cytoplasm and the host cell to transport effector proteins that manipulate cellular processes to benefit the pathogen. IpaB and IpaD form a tip complex atop the TTSA needle and are required for pathogenesis. Because they are common to all virulent Shigella spp., they are ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We examined the immunogenicity and protective efficacy of IpaB and IpaD, alone or combined, coadministered with a double mutant heat-labile toxin (dmLT) from Escherichia coli, used as a mucosal adjuvant, in a mouse model of intranasal immunization and pulmonary challenge. Robust systemic and mucosal antibody-and T cell-mediated immunities were induced against both proteins, particularly IpaB. Mice immunized in the presence of dmLT with IpaB alone or IpaB combined with IpaD were fully protected against lethal pulmonary infection with Shigella flexneri and Shigella sonnei. We provide the first demonstration that the Shigella TTSAs IpaB and IpaD are promising antigens for the development of a cross-protective Shigella vaccine.

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“…Muramyl dipeptide is the smallest component of PGN which is recognized by PRRs. Peptidoglycan, a ligand of TLR2, induces Th1-polarized IRs, enhancing protection against fatal infection with Yersinia pestis in mice (28). Moreover, MDP is an NOD2 ligand.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, these mice were protected from lethal infection with Y. pestis (28). Protection was thought to be mediated by binding of PGN to TLR-2.…”

mentioning

confidence: 96%

Effect of Heat-Killed Escherichia coli, Lipopolysaccharide, and Muramyl Dipeptide Treatments on the Immune Response Phenotype and Allergy in Neonatal Pigs Sensitized to the Egg White Protein Ovomucoid

Schmied

Rupa

Garvie

et al. 2012

Clin Vaccine Immunol

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Predisposition to food allergies may reflect a type 2 immune response (IR) bias in neonates due to the intrauterine environment required to maintain pregnancy. The hygiene hypothesis states that lack of early environmental stimulus leading to inappropriate development and bias in IR may also contribute. Here, the ability of heat-killed Escherichia coli, lipopolysaccharide (LPS), or muramyl dipeptide (MDP) to alter IR bias and subsequent allergic response in neonatal pigs was investigated. Three groups of three litters of pigs (12 pigs/litter) were given intramuscular injections of E. coli, LPS, MDP, or phosphate-buffered saline (PBS) (control) and subsequently sensitized to the egg white allergen ovomucoid using an established protocol. To evaluate change in IR bias, immunoglobulin isotype-associated antibody activity (AbA), concentrations of type 1 and 2 and proinflammatory cytokines released from mitogen-stimulated blood mononuclear cells, and the percentage of T-regulatory cells (T-regs) in blood were measured. Clinical signs of allergy were assessed after oral challenge with egg white. The greatest effect on IR bias was observed in MDP-treated pigs, which had a type 2-biased phenotype by isotype-specific AbA, cytokine production, and a low proportion of T-regs. LPS-treated pigs had decreased type 1-and type 2-associated AbA. E. coli-treated pigs displayed increased response to Ovm as AbA and had more balanced cytokine profiles, as well as the highest proportion of T-regs. Accordingly, pigs treated with MDP were more susceptible to allergy than PBS controls, while pigs treated with LPS were less susceptible. Treatment with E. coli did not significantly alter the frequency of clinical signs.

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Neonatal mucosal immunization with a non-living, non-genetically modified Lactococcus lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection

Cited by 87 publications

References 37 publications

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

Effect of Heat-Killed Escherichia coli, Lipopolysaccharide, and Muramyl Dipeptide Treatments on the Immune Response Phenotype and Allergy in Neonatal Pigs Sensitized to the Egg White Protein Ovomucoid

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