A novel intranasal Protollin™-based measles vaccine induces mucosal and systemic neutralizing antibody responses and cell-mediated immunity in mice

Chabot, Sophie; Brewer, Angela; Lowell, George H.; Plante, Martin; Cyr, Sonya; Burt, David S.; Ward, Brian J.

doi:10.1016/j.vaccine.2004.09.010

Cited by 47 publications

(21 citation statements)

References 40 publications

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“…They include the well-known cholera toxin and Escherichia coli heat-labile toxin as well as their non-toxic variants, muramyl di-peptide [3], outer membrane proteins [4,5] and outer membrane vesicles [6] of e.g. Neisseria meningitidis.…”

Section: Introductionmentioning

confidence: 99%

Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization

Audouy¹,

Roosmalen²,

Neef³

et al. 2006

Vaccine

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Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractThe present work reports the use of non-living non-recombinant bacteria as a delivery system for mucosal vaccination. Antigens are bound to the cell-wall of pretreated Lactococcus lactis, designated as Gram-positive enhancer matrix (GEM), by means of a peptidoglycan binding domain. The influence of the GEM particles on the antigen-specific serum antibody response was studied. Following nasal immunization with the GEM-based vaccines, antibody responses were induced at systemic and local levels. Furthermore, different GEM-based vaccines could be used consecutively in the same mice without adverse effects or loss of activity. Taken together, the results evidence the adjuvant properties of the GEM particles and indicate that GEM-based vaccines can be used repeatedly and are particularly suitable for nasal immunization purposes.

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Section: Introductionmentioning

confidence: 99%

Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization

Audouy¹,

Roosmalen²,

Neef³

et al. 2006

Vaccine

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“…Early proof-of-principal studies with EtpA were conducted using an intranasal route of vaccination with Protollin (14,[17][18][19] or heat-labile toxin (LT) (20). However, because LT is not safe for intranasal vaccination in humans (21,22), and because an LT toxoid will likely be a key component of next-generation vaccines, here we investigated the immunogenicity and protective efficacy …”

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confidence: 99%

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Luo

Vickers

Fleckenstein

2016

Clin Vaccine Immunol

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c Enterotoxigenic Escherichia coli (ETEC) strains are a common cause of diarrhea. Extraordinary antigenic diversity has prompted a search for conserved antigens to complement canonical approaches to ETEC vaccine development. EtpA, an immunogenic extracellular ETEC adhesin relatively conserved in the ETEC pathovar, has previously been shown to be a protective antigen following intranasal immunization. These studies were undertaken to explore alternative routes of EtpA vaccination that would permit use of a double mutant (R192G L211A) heat-labile toxin (dmLT) adjuvant. Here, oral vaccination with EtpA adjuvanted with dmLT afforded significant protection against small intestinal colonization, and the degree of protection correlated with fecal IgG, IgA, or total fecal antibody responses to EtpA. Sublingual vaccination yielded compartmentalized mucosal immune responses with significant increases in anti-EtpA fecal IgG and IgA, and mice vaccinated via this route were also protected against colonization. In contrast, while intradermal (i.d.) vaccination achieved high levels of both serum and fecal antibodies against both EtpA and dmLT, mice vaccinated via the i.d. route were not protected against subsequent colonization and the avidity of serum IgG and IgA EtpA-specific antibodies was significantly lower after i.d. immunization compared to other routes. Finally, we demonstrate that antiserum from vaccinated mice significantly impairs binding of LT to cognate GM1 receptors and shows near complete neutralization of toxin delivery by ETEC in vitro. Collectively, these data provide further evidence that EtpA could complement future vaccine strategies but also suggest that additional effort will be required to optimize its use as a protective immunogen. Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness in developing countries, where young children are most susceptible (1, 2). In addition, these pathogens are also a common cause of diarrhea in immunologically naive travelers (3) who venture to areas of endemicity where sanitation and clean water remain limited.Given the significant impact of ETEC on global health, a vaccine to prevent these infections is a significant priority (4). However, despite decades of investigative efforts following the discovery of toxin-producing E. coli in patients with clinical illnesses indistinguishable from cholera (5), a vaccine that affords broadbased protection has yet to be developed.All of the ETEC-specific virulence genes described to date are encoded on plasmids. These include the heat-labile and/or heatstable enterotoxins that define this pathovar and the colonization factors (CFs). Most vaccines to date have primarily targeted these colonization factors, which include a broad array of fimbrial as well as afimbrial surface antigens thought to be essential for intestinal colonization and/or heat-labile toxin.Unfortunately, the heterogeneity of CF antigenic structures presents a challenge to development of a broadly protective vaccine. ...

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“…In this context, we examined the immunomodulatory potential of Protollin, a mucosal vaccine adjuvant composed of TLR2 and TLR4 ligands, in a murine model of experimental allergic asthma (11). Protollin was determined to be safe and well-tolerated up to a dose of 1.5 mg LPS when administered via the intranasal route in phase I (12) and II (13) human clinical trials, and has been tested as an intranasal vaccine adjuvant in animal models of influenza (14), respiratory syncytial virus (15), severe acute respiratory syndrome (16), plague (Yersinia pestis) (17), and measles (18) infection, as well as in models of Alzheimer's disease (19). Protollin consists of LPS molecules (TLR4 ligand) from Shigella flexneri, a Gram-negative bacterium, noncovalently incorporated in nanomolecular vesicles formed by proteosomes, consisting of purified hydrophobic outer-membrane proteins from Neisseria meningitidis (shown to signal via a TLR2/1 heterodimer complex) (20,21).…”

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confidence: 99%

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Shalaby

Nakada

et al. 2012

The Journal of Immunology

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Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2−/−, or Tlr4−/− BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges. Nasal application of Protollin or Protollin admixed with BPEx was sufficient to inhibit allergic lower airway disease with minimal collateral lung inflammation. Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4+Foxp3+ and CD4+Foxp3− T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs. Adoptive transfer of cervical LN CD4+ICOS+, but not CD4+ICOS−, cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia. Thus, our data indicate that expansion of resident ICOS-expressing CD4+ T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.

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A novel intranasal Protollin™-based measles vaccine induces mucosal and systemic neutralizing antibody responses and cell-mediated immunity in mice

Cited by 47 publications

References 40 publications

Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization

Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

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