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 Polymeric Caffeic Acid Acts as a Nasal Vaccine Formulation against Streptococcus pneumoniae Infections in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 585
Author(s):  
Rui Tada ◽  
Hidehiko Suzuki ◽  
Miki Ogasawara ◽  
Daisuke Yamanaka ◽  
Yoshiyuki Adachi ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Caffeic Acid ◽  
Pathogenic Bacteria ◽  
Protein A ◽  
Surface Protein ◽  
Mucosal Vaccine ◽  
Vaccine Formulation ◽  
Protective Effects ◽  
Mucosal Adjuvant ◽  
Nasal Vaccine

Infectious diseases are the second leading cause of death worldwide, highlighting the importance of the development of a novel and improved strategy for fighting pathogenic microbes. Streptococcus pneumoniae is a highly pathogenic bacteria that causes pneumonia with high mortality rates, especially in children and elderly individuals. To solve these issues, a mucosal vaccine system would be the best solution for the prevention and treatment of these diseases. We have recently reported that enzymatically polymerized caffeic acid (pCA) acts as a mucosal adjuvant when co-administered with antigenic proteins via the nasal route. Moreover, the sources of caffeic acid and horseradish peroxidase are ingredients found commonly in coffee beans and horseradish, respectively. In this study, we aimed to develop a pneumococcal nasal vaccine comprising pneumococcal surface protein A (PspA) and pCA as the mucosal adjuvant. Intranasal immunization with PspA and pCA induced the production of PspA-specific antibody responses in the mucosal and systemic compartments. Furthermore, the protective effects were tested in a murine model of S. pneumoniae infection. Intranasal vaccination conferred antigen-dependent protective immunity against a lethal infection of S. pneumoniae. In conclusion, pCA is useful as a serotype-independent universal nasal pneumococcal vaccine formulation.

scholarly journals High-Resolution Quantitative Mapping of Macaque Cervicovaginal Epithelial Thickness: Implications for Mucosal Vaccine Delivery

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathleen L. Vincent ◽  
Patrice A. Frost ◽  
Massoud Motamedi ◽  
Edward J. Dick ◽  
Jingna Wei ◽  
...  
Keyword(s):  
High Resolution ◽  
Immune Responses ◽  
Real Time ◽  
Basal Layer ◽  
Mucosal Vaccine ◽  
P Value ◽  
Mechanical Abrasion ◽  
Mucosal Vaccination ◽  
Epithelial Thickness ◽  
Oct Imaging

Vaginal mucosal surfaces naturally offer some protection against sexually transmitted infections (STIs) including Human Immunodeficiency Virus-1, however topical preventative medications or vaccine designed to boost local immune responses can further enhance this protection. We previously developed a novel mucosal vaccine strategy using viral vectors integrated into mouse dermal epithelium to induce virus-specific humoral and cellular immune responses at the site of exposure. Since vaccine integration occurs at the site of cell replication (basal layer 100-400 micrometers below the surface), temporal epithelial thinning during vaccine application, confirmed with high resolution imaging, is desirable. In this study, strategies for vaginal mucosal thinning were evaluated noninvasively using optical coherence tomography (OCT) to map reproductive tract epithelial thickness (ET) in macaques to optimize basal layer access in preparation for future effective intravaginal mucosal vaccination studies. Twelve adolescent female rhesus macaques (5-7kg) were randomly assigned to interventions to induce vaginal mucosal thinning, including cytobrush mechanical abrasion, the chemical surfactant spermicide nonoxynol-9 (N9), the hormonal contraceptive depomedroxyprogesterone acetate (DMPA), or no intervention. Macaques were evaluated at baseline and after interventions using colposcopy, vaginal biopsies, and OCT imaging, which allowed for real-time in vivo visualization and measurement of ET of the mid-vagina, fornices, and cervix. P value ≤0.05 was considered significant. Colposcopy findings included pink, rugated tissue with variable degrees of white-tipped, thickened epithelium. Baseline ET of the fornices was thinner than the cervix and vagina (p<0.05), and mensing macaques had thinner ET at all sites (p<0.001). ET was decreased 1 month after DMPA (p<0.05) in all sites, immediately after mechanical abrasion (p<0.05) in the fornix and cervix, and after two doses of 4% N9 (1.25ml) applied over 14 hrs in the fornix only (p<0.001). Histological assessment of biopsied samples confirmed OCT findings. In summary, OCT imaging allowed for real time assessment of macaque vaginal ET. While varying degrees of thinning were observed after the interventions, limitations with each were noted. ET decreased naturally during menses, which may provide an ideal opportunity for accessing the targeted vaginal mucosal basal layers to achieve the optimum epithelial thickness for intravaginal mucosal vaccination.

scholarly journals Intranasal Immunization with Gal-Inhibitable Lectin plus an Adjuvant of CpG Oligodeoxynucleotides Protects against Entamoeba histolytica Challenge

2007 ◽  
Vol 75 (10) ◽  
pp. 4917-4922 ◽  
Author(s):  
Catherine P. A. Ivory ◽  
Kris Chadee
Keyword(s):  
Immune Responses ◽  
Entamoeba Histolytica ◽  
Mucosal Vaccine ◽  
Target Cells ◽  
Cpg Odn ◽  
Mucosal Vaccination ◽  
Humoral Immune ◽  
Cpg Oligodeoxynucleotides ◽  
Humoral Immune Responses

ABSTRACT The development of an effective amebiasis vaccine could improve child health in the developing world, reducing cases of amebic colitis and liver abscess. An ideal vaccine would be comprised of a well-characterized parasite antigen and an adjuvant, which would have high potency while driving the immune response in a Th1 direction. This study describes a mucosal vaccine composed of the Entamoeba histolytica galactose/N-acetyl-d-galactosamine-inhibitable lectin (Gal-lectin) and CpG oligodeoxynucleotides (CpG-ODN). The Gal-lectin is a protein involved in parasite virulence and adherence and is known to activate immune cells, while CpG-ODN are known to be potent inducers of type 1-like immune responses. We demonstrated that intranasal administration of the vaccine resulted in strong Gal-lectin-specific Th1 responses and humoral responses. Vaccination induced the production of Gal-lectin-specific T cells and the production of the proinflammatory cytokine gamma interferon. Vaccinated animals had detectable serum anti-Gal-lectin immunoglobulin G (IgG) and stool anti-Gal-lectin IgA capable of blocking parasite adherence to target cells in vitro. One week after immunization, gerbils were challenged intrahepatically with live trophozoites. Vaccinated gerbils had no detectable abscesses after day 5, whereas control gerbils developed larger abscesses. These results show that mucosal vaccination with Gal-lectin and CpG-ODN can induce both systemic and humoral immune responses.

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.

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.

scholarly journals Bacterial Endotoxins and Their Role in Periparturient Diseases of Dairy Cows: Mucosal Vaccine Perspectives

Dairy ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 61-90
Author(s):  
Emily F. Eckel ◽  
Burim N. Ametaj
Keyword(s):  
Infectious Diseases ◽  
Dairy Cows ◽  
Rumen Fluid ◽  
Systemic Circulation ◽  
Mucosal Vaccine ◽  
Low Grade ◽  
Mucosal Vaccination ◽  
Inflammatory Conditions ◽  
Milk Fever ◽  
Bacterial Endotoxins

During the periparturient period there is a significant increase in the incidence of multiple metabolic and infectious diseases in dairy cows. Dairy cows are fed high-grain diets immediately after calving to support production of large amounts of milk. Mounting evidence indicates these types of diets are associated with the release of high amounts of endotoxins in the rumen fluid. If infected, the udder and uterus additionally become important sources of endotoxins during the postpartum period. There is increasing evidence that endotoxins translocate from rumen, uterus, or udder into the systemic circulation and trigger chronic low-grade inflammatory conditions associated with multiple diseases including fatty liver, mastitis, retained placenta, metritis, laminitis, displaced abomasum, milk fever, and downer cow syndrome. Interestingly, endotoxin-related diseases are triggered by a bacterial component and not by a specific bacterium. This makes prevention of these type of diseases different from classical infectious diseases. Prevention of translocation of endotoxins into the host systemic circulation needs to take priority and this could be achieved with a new approach: mucosal vaccination. In this review article, we discuss all the aforementioned issues in detail and also report some of our trials with regards to mucosal vaccination of periparturient dairy cows.

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.

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 Mucosal Adjuvant Properties of the Shigella Invasin Complex

2006 ◽  
Vol 74 (5) ◽  
pp. 2856-2866 ◽  
Author(s):  
Robert W. Kaminski ◽  
K. Ross Turbyfill ◽  
Edwin V. Oaks
Keyword(s):  
Immune Responses ◽  
Binding Capacity ◽  
Lymphoid Cells ◽  
Mucosal Vaccine ◽  
Vaccine Antigen ◽  
Interleukin 4 ◽  
Cell Binding ◽  
Th2 Response ◽  
Mucosal Adjuvant ◽  
Mucosal Antibody

ABSTRACT The Shigella invasin complex (Invaplex) is an effective mucosal vaccine capable of protecting against Shigella challenge in animal models. The major antigenic constituents of Invaplex are the Ipa proteins and lipopolysaccharide. The cell-binding capacity of the Ipa proteins prompted the investigation into the adjuvanticity of Invaplex. Using ovalbumin (OVA) as a model antigen, intranasal immunization with OVA combined with Invaplex was found to enhance anti-OVA serum immunoglobulin G (IgG) and IgA responses and induce OVA-specific mucosal antibody responses at sites located both proximal and distal to the immunization site. The immune responses induced with OVA and Invaplex were comparable in both magnitude and duration to the immune responses induced after immunization with OVA and cholera toxin. The OVA-specific immune response was characterized by high levels of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5, or IL-10 from lymphoid cells of immunized animals, suggesting a Th2 response. In addition to enhancing the immunogenicity of OVA, Invaplex-specific immune responses were also induced, indicating the potential for the development of a combination vaccine consisting of Invaplex and other immunogens. Preexisting Invaplex-specific immunity did not interfere with the capacity to enhance the immunogenicity of a second, unrelated vaccine antigen, suggesting that Invaplex could be used as a mucosal adjuvant in multiple vaccine regimens.

Sign in / Sign up

Export Citation Format

Share Document