Polymeric Caffeic Acid Is a Safer Mucosal Adjuvant That Augments Antigen-Specific Mucosal and Systemic Immune Responses in Mice

2018 ◽  
Vol 15 (9) ◽  
pp. 4226-4234 ◽  
Author(s):  
Rui Tada ◽  
Daisuke Yamanaka ◽  
Miki Ogasawara ◽  
Momoko Saito ◽  
Naohito Ohno ◽  
...  
Keyword(s):  
Immune Responses ◽  
Caffeic Acid ◽  
Mucosal Adjuvant

scholarly journals Enzymatically polymerised polyphenols prepared from various precursors potentiate antigen-specific immune responses in both mucosal and systemic compartments in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246422
Author(s):  
Rui Tada ◽  
Miki Ogasawara ◽  
Daisuke Yamanaka ◽  
Yasuhiro Sakurai ◽  
Yoichi Negishi ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Caffeic Acid ◽  
Intranasal Administration ◽  
Lavage Fluid ◽  
Modern Medicine ◽  
Mucosal Vaccine ◽  
Mucosal Adjuvant ◽  
Mucosal Vaccination ◽  
Nasal Vaccine

Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.

scholarly journals Maternal immune status influences HIV-specific immune responses in pups after DNA prime protein boost using mucosal adjuvant

Vaccine ◽  
2008 ◽  
Vol 26 (47) ◽  
pp. 5957-5966 ◽  
Author(s):  
Andreas Bråve ◽  
Kari Johansen ◽  
Paolo Palma ◽  
Reinhold Benthin ◽  
Jorma Hinkula
Keyword(s):  
Immune Responses ◽  
Immune Status ◽  
Mucosal Adjuvant ◽  
Protein Boost

scholarly journals Recombinant Norwalk Virus-Like Particles Administered Intranasally to Mice Induce Systemic and Mucosal (Fecal and Vaginal) Immune Responses

2001 ◽  
Vol 75 (20) ◽  
pp. 9713-9722 ◽  
Author(s):  
Roberto A. Guerrero ◽  
Judith M. Ball ◽  
Sharon S. Krater ◽  
Susan E. Pacheco ◽  
John D. Clements ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oral Route ◽  
Soluble Proteins ◽  
Mucosal Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Doses ◽  
Norwalk Virus ◽  
Mucosal Adjuvant ◽  
Virus Like Particles ◽  
Serum Igg

ABSTRACT Recombinant Norwalk virus-like particles (rNV VLPs) were administered to BALB/c mice by the intranasal (i.n.) route to evaluate the induction of mucosal antibody responses. The results were compared to systemic and mucosal responses observed in new and previous studies (J. M. Ball, M. E. Hardy, R. L. Atmar, M. E. Connor, and M. K. Estes, J. Virol. 72:1345–1353, 1998) after oral administration of rNV VLPs. Immunizations were given in the presence or absence of a mucosal adjuvant, mutant Escherichia coliheat-labile toxin LT(R192G). rNV-specific immunoglobulin G (IgG) and fecal IgA were evaluated by enzyme-linked immunosorbent assay. The i.n. delivery of rNV VLPs was more effective than the oral route at inducing serum IgG and fecal IgA responses to low doses of rNV particles. Vaginal responses of female mice given VLPs by the i.n. and oral routes were also examined. All mice that received two immunizations with low doses i.n. (10 or 25 μg) of rNV VLPs and the majority of mice that received two high doses orally (200 μg) in the absence of adjuvant had rNV-specific serum IgG, fecal, and vaginal responses. Additional experiments evaluated whether rNV VLPs can function as a mucosal adjuvant by evaluating the immune responses to two soluble proteins, keyhole limpet hemocyanin and chicken egg albumin. Under the conditions tested, rNV VLPs did not enhance the serum IgG or fecal IgA response to these soluble proteins when coadministered by the i.n. or oral route. Low doses of nonreplicating rNV VLPs are immunogenic when administered i.n. in the absence of adjuvant, and addition of adjuvant enhanced the magnitude and duration of these responses. Recombinant NV VLPs represent a candidate mucosal vaccine for NV infections in humans.

Fibroblast-stimulating lipopeptide-1 as a potential mucosal adjuvant enhances mucosal and systemic immune responses to enterovirus 71 vaccine

Vaccine ◽  
2018 ◽  
Vol 36 (29) ◽  
pp. 4331-4338 ◽  
Author(s):  
Yu-Li Lin ◽  
Pei-Yun Cheng ◽  
Chiao-Li Chin ◽  
Li-Min Huang ◽  
Shr-Yu Lin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Enterovirus 71 ◽  
Mucosal Adjuvant

Mucosal and systemic immune responses of mice to tetanus toxoid coadministered nasally with AFCo1

2011 ◽  
Vol 57 (3) ◽  
pp. 256-261 ◽  
Author(s):  
Belkis Romeu ◽  
Elyzabeth González ◽  
Judith del Campo ◽  
Reynaldo Acevedo ◽  
Caridad Zayas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvants ◽  
Mucosal Adjuvant ◽  
Mucosal Vaccines ◽  
Nasal Immunization ◽  
Human Use ◽  
Vaginal Wash ◽  
Systemic Compartment

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity. However, few mucosal vaccine adjuvants are currently approved for human use. Neisseria meningitidis B proteoliposome-derived cochleate (AFCo1 — Adjuvant Finlay Cochleate 1) has been demonstrated to be a potent mucosal adjuvant. The present work demonstrates that intranasal immunization of 3 doses of tetanus toxoid (TT) coadministered with AFCo1 in mice promotes high systemic and mucosal responses. The anti-TT IgG serum titers and the mucosal anti-TT IgA in saliva and vaginal wash were significantly higher than TT alone. The analysis of antibody subclasses showed that intranasal administration of AFCo1 + TT induced not only IgG1 but also IgG2a anti-TT antibodies at levels comparable to those obtained with TT vaccine (vax-TET). These data support the fact that AFCo1 is a potent mucosal adjuvant in nasal immunization to a coadministered protein antigen.

Caffeic Acid–coated Nanolayer on Mineral Trioxide Aggregate Potentiates the Host Immune Responses, Angiogenesis, and Odontogenesis

2020 ◽  
Vol 46 (10) ◽  
pp. 1455-1464 ◽  
Author(s):  
Ming-Gene Tu ◽  
Alvin Kai-Xing Lee ◽  
Yen-Hong Lin ◽  
Tsui-Hsien Huang ◽  
Chia-Che Ho ◽  
...  
Keyword(s):  
Immune Responses ◽  
Caffeic Acid ◽  
Mineral Trioxide Aggregate ◽  
Host Immune Responses

scholarly journals A Double Mutant Heat-Labile Toxin from Escherichia coli, LT(R192G/L211A), Is an Effective Mucosal Adjuvant for Vaccination against Helicobacter pylori Infection

2013 ◽  
Vol 81 (5) ◽  
pp. 1532-1540 ◽  
Author(s):  
Louise Sjökvist Ottsjö ◽  
Carl-Fredrik Flach ◽  
John Clements ◽  
Jan Holmgren ◽  
Sukanya Raghavan
Keyword(s):  
Escherichia Coli ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Double Mutant ◽  
Bacterial Load ◽  
Mucosal Vaccine ◽  
Mucosal Adjuvant ◽  
Content Type ◽  
Heat Labile ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection in the stomach is a common cause of peptic ulcer disease and is a strong risk factor for the development of gastric adenocarcinoma, yet no effective vaccine againstH. pyloriinfection is available to date. In mice, mucosal vaccination withH. pyloriantigens when given together with cholera toxin (CT) adjuvant, but not without adjuvant, can induce protective immune responses againstH. pyloriinfection. However, the toxicity of CT precludes its use as a mucosal adjuvant in humans. We evaluated a recently developed, essentially nontoxic double mutantEscherichia coliheat-labile toxin, LT(R192G/L211A) (dmLT), as a mucosal adjuvant in an experimentalH. pylorivaccine and compared it to CT in promoting immune responses and protection againstH. pyloriinfection in mice. Immunization via the sublingual or intragastric route withH. pylorilysate antigens and dmLT resulted in a significant decrease in bacterial load after challenge compared to that in unimmunized infection controls and to the same extent as when using CT as an adjuvant. Cellular immune responses in the sublingually immunized mice known to correlate with protection were also fully comparable when using dmLT and CT as adjuvants, resulting in enhancedin vitroproliferative and cytokine responses from spleen and mesenteric lymph node cells toH. pyloriantigens. Our results suggest that dmLT is an attractive adjuvant for inclusion in a mucosal vaccine againstH. pyloriinfection.

scholarly journals Zonula Occludens Toxin Acts as an Adjuvant through Different Mucosal Routes and Induces Protective Immune Responses

2003 ◽  
Vol 71 (4) ◽  
pp. 1897-1902 ◽  
Author(s):  
Mariarosaria Marinaro ◽  
Alessio Fasano ◽  
Maria Teresa De Magistris
Keyword(s):  
Immune Responses ◽  
Tight Junctions ◽  
Mucosal Permeability ◽  
Mucosal Adjuvant ◽  
Promising Tool ◽  
Zonula Occludens ◽  
Specific Serum ◽  
Mucosal Vaccines ◽  
Zonula Occludens Toxin ◽  
Putative Binding Site

ABSTRACT Zonula occludens toxin (Zot) is produced by Vibrio cholerae and has the ability to increase mucosal permeability by reversibly affecting the structure of tight junctions. Because of this property, Zot is a promising tool for mucosal drug and antigen (Ag) delivery. Here we show that Zot acts as a mucosal adjuvant to induce long-lasting and protective immune responses upon mucosal immunization of mice. Indeed, the intranasal delivery of ovalbumin with two different recombinant forms of Zot in BALB/c mice resulted in high Ag-specific serum immunoglobulin G titers that were maintained over the course of a year. Moreover, His-Zot induced humoral and cell-mediated responses to tetanus toxoid in C57BL/6 mice and protected the mice against a systemic challenge with tetanus toxin. In addition, we found that Zot also acts as an adjuvant through the intrarectal route and that it has very low immunogenicity compared to the adjuvant Escherichia coli heat-labile enterotoxin. Finally, by using an octapeptide representing the putative binding site of Zot and of its endogenous analogue zonulin, we provide evidence that Zot may bind a mucosal receptor on nasal mucosa and may mimic an endogenous regulator of tight junctions to deliver Ags in the submucosa. In conclusion, Zot is a novel and effective mucosal adjuvant that may be useful for the development of mucosal vaccines.

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