A single nasal dose of fms-like tyrosine kinase receptor-3 ligand, but not peritoneal application, enhances nontypeable Haemophilus influenzae-specific long-term mucosal immune responses in the nasopharynx

Kodama, Satoru; Hirano, Takashi; Noda, Kenji; Abe, Nobuyuki; Suzuki, Masashi

doi:10.1016/j.vaccine.2010.01.043

Cited by 17 publications

(23 citation statements)

References 44 publications

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“…In contrast to those studies, Kodama et al used an entirely different immunization protocol [69]. In their study, 10 μ g rFlt3L was delivered alone on day 0 and antigen alone ( Haemophilus influenzae P6) was delivered on days 6, 13, and 20.…”

Section: Flt3 Ligandmentioning

confidence: 99%

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Cytokines: The Future of Intranasal Vaccine Adjuvants

Thompson

Staats

2011

Clinical and Developmental Immunology

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Due to its potential as an effective, needle-free route of immunization for use with subunit vaccines, nasal immunization continues to be evaluated as a route of immunization in both research and clinical studies. However, as with other vaccination routes, subunit vaccines often require the addition of adjuvants to induce potent immune responses. Unfortunately, many commonly used experimental vaccine adjuvants, such as cholera toxin and E. coli heat-labile toxin, are too toxic for use in humans. Because new adjuvants are needed, cytokines have been evaluated for their ability to provide effective adjuvant activity when delivered by the nasal route in both animal models and in limited human studies. It is the purpose of this paper to discuss the potential of cytokines as nasal vaccine adjuvants.

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Section: Flt3 Ligandmentioning

confidence: 99%

“…The four studies that investigated the ability of Flt3L to increase serum immune responses also evaluated its ability to increase mucosal immune responses [28, 29, 68, 69]. Two studies have demonstrated enhanced mucosal antibody production following vaccination with Flt3L.…”

Section: Flt3 Ligandmentioning

confidence: 99%

Cytokines: The Future of Intranasal Vaccine Adjuvants

Thompson

Staats

2011

Clinical and Developmental Immunology

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“…This approach may potentially lower the amount of antigen required to induce protection and may also lower the incidence of adverse side effects reported for WIVs. In most studies soluble cytokines have been administered in μg amounts, which is clearly well in excess of the amounts utilized in the present study; albeit the total number of doses and dosing schedules vary significantly depending on the study (reviewed extensively in [8,10]. It should be noted that soluble IL-23 has been reported to have adverse effects such as inducing chronic inflammation and autoimmune disease [34,35] and both antitumor and tumor promoting effects [36,37].…”

Section: Resultsmentioning

confidence: 99%

“…Cytokines have great potential to serve as potent and specific adjuvants due to their diverse role in immune responses [6,7]. They are actively being evaluated for use as adjuvants for intranasal vaccine formulations [8] and have been used extensively as soluble adjuvants co-administered with numerous vaccines [9,10], or in a fused or linked form directly with antigen [7,11]. The superior immunogenicity of WIV as compared to split or subunit influenza vaccines [12,13] encouraged us to utilize WIV bearing cytokines as a more immunogenic vaccine formulation.…”

Section: Introductionmentioning

confidence: 99%

Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines

Khan

Heffron

High

2014

Virol J

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BackgroundPotent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge.FindingsHere, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes.ConclusionsThis study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

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“…we have recently reported that nasal immunization combined with fms-like tyrosine kinase receptor-3 ligand (Flt3L) or a-galactosylceramide (a-GalCer) induced P6-specific immune responses [12,13]. These adjuvants, including CpG ODN, Flt3L, and a-GalCer, are non-toxic for humans, and they induce and stimulate mature DCs.…”

Section: Discussionmentioning

confidence: 99%