Monophosphoryl lipid A enhances nontypeable Haemophilus influenzae-specific mucosal and systemic immune responses by intranasal immunization

Iwasaki, Takaya; Hirano, Takashi; Kodama, Satoru; Kadowaki, Yoshinori; Moriyama, Masaya; Kawano, Toshiaki; Suzuki, Masashi

doi:10.1016/j.ijporl.2017.03.018

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…The activation of TLRs in APCs can modulate the development of both humoral and cellular adaptive immune responses, making the TLRs expressed in APCs attractive targets for the development of vaccine adjuvants [ 20 ]. In this regard, it was reported that the nasal administration of antigens from respiratory pathogens together with the TLR4 agonist monophosphoryl lipid A stimulated a specific Th1 response and IgA production in the respiratory tract [ 21 , 22 ]. The synthetic analog of double-stranded RNA and TLR3 agonist poly (I:C) [ 23 , 24 ], and the TLR9 agonist unmethylated CpG oligodeoxynucleotide [ 25 ] were also shown to enhance the activity of APCs and improve IgA production in the respiratory mucosa.…”

Section: Discussionmentioning

confidence: 99%

The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines

et al. 2023

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Previously, we demonstrated that nasally administered Corynebacterium pseudodiphteriticum 090104 (Cp) or its bacterium-like particles (BLPs) increase the resistance of mice against bacterial and viral respiratory pathogens by modulating the innate immunity. In this work, we evaluated the ability of Cp and BLPs to stimulate alveolar macrophages, and to enhance the humoral immune response induced by a commercial vaccine against Streptococcus pneumoniae. In the first set of experiments, Cp or the BLPs were incubated with primary cultures of murine alveolar macrophages and the phagocytic activity, and the production of cytokines was evaluated. The results revealed that Cp and BLPs were efficiently phagocyted by respiratory macrophages and that both treatments triggered the production of TNF-α, IFN-γ, IL-6, and IL-1β. In the second set of experiments, 3-week-old Swiss mice were intranasally immunized at days 0, 14, and 28 with the pneumococcal vaccine Prevenar®13 (PCV), Cp + PCV, or BLPs + PCV. On day 33, samples of bronco-alveolar lavages (BAL) and serum were collected for the study of specific antibodies. In addition, immunized mice were challenged with S. pneumoniae serotypes 6B or 19F on day 33 and sacrificed on day 35 (day 2 post-infection) to evaluate the resistance to the infection. Both Cp + PCV and BLPs + PCV groups had higher specific serum IgG and BAL IgA antibodies than the PCV control mice. In addition, the mice that were immunized with Cp + PCV or BLPs + PCV had lower lung and blood pneumococcal cell counts as well as lower levels of BAL albumin and LDH, indicating a reduced lung damage compared to the control mice. Improved levels of anti-pneumococcal antibodies were also detected in the serum and BAL samples after the challenges with the pathogens. The results demonstrated that C. pseudodiphteriticum 090104 and its bacterium-like particles are capable of stimulating the respiratory innate immune system serving as adjuvants to potentiate the adaptive humoral immune response. Our study is a step forward in the positioning of this respiratory commensal bacterium as a promising mucosal adjuvant for vaccine formulations aimed at combating respiratory infectious diseases.

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Section: Discussionmentioning

confidence: 99%

The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines

et al. 2023

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“…Future studies need to explore the genetic and environmental interrelationships of these polymorphisms and their impact on predisposition or susceptibility to OM and its severity. Next generation sequencing and large, well-phenotyped populations from multiple regions will expand the applicability of these data to support development of new treatment strategies that may enhance innate immunity such as monophosphoryl lipid A (MPL) studies in mice (Iwasaki et al, 2017), b-defensin 2 and probiotics or alter the activation of the innate immune responses to reduce inflammation and chronic OM pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Innate Immunity in the Middle Ear Mucosa

Massa

Spann

Cripps

2021

Front. Cell. Infect. Microbiol.

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Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.

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“…A series of additional studies confirmed the importance and effectiveness of nasal vaccination, as well as the need to incorporate molecules that manage to enhance the immune response. Preclinical studies of the last decade ensure the validity of IN vaccination in several diseases, such as acute otitis [116] , ebola virus disease [117] , cutaneous leishmaniasis [118] and tetanus [67] ( Table 2 ). Moreover, as mentioned above, clinical trials have assured the safety of vaccine formulations for meningitis [17] , diphtheria [119] , HIV [120] and respiratory disease from parainfluenza [121] ( Table 3 ).…”

Section: Preclinical and Clinical Studies On Nasal Vaccinesmentioning

confidence: 99%

Advances in intranasal vaccine delivery: A promising non-invasive route of immunization

Kehagia,

Papakyriakopoulou,

Valsami

2023

Vaccine

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Monophosphoryl lipid A enhances nontypeable Haemophilus influenzae-specific mucosal and systemic immune responses by intranasal immunization

Cited by 6 publications

References 31 publications

The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines

The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines

Innate Immunity in the Middle Ear Mucosa

Advances in intranasal vaccine delivery: A promising non-invasive route of immunization

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