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 Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus

2010 ◽  
Vol 84 (24) ◽  
pp. 12703-12712 ◽  
Author(s):  
Hiroyuki Kayamuro ◽  
Yasuo Yoshioka ◽  
Yasuhiro Abe ◽  
Shuhei Arita ◽  
Kazufumi Katayama ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Interleukin 1 ◽  
Influenza Virus Infection ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvants ◽  
Mucosal Surfaces ◽  
Mucosal Vaccines ◽  
Etiological Agents ◽  
Family Cytokine

ABSTRACT A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W v mice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.

scholarly journals Mucosal Vaccine Development Based on Liposome Technology

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Valentina Bernasconi ◽  
Karin Norling ◽  
Marta Bally ◽  
Fredrik Höök ◽  
Nils Y. Lycke
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Recent Progress ◽  
Vaccine Development ◽  
Mucosal Vaccine ◽  
Limiting Factor ◽  
Successful Development ◽  
Mucosal Vaccines ◽  
Increasing Demand ◽  
Portal Of Entry

Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines.

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.

scholarly journals Cytokines: The Future of Intranasal Vaccine Adjuvants

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Afton L. Thompson ◽  
Herman F. Staats
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Clinical Studies ◽  
Vaccine Adjuvants ◽  
Adjuvant Activity ◽  
Subunit Vaccines ◽  
E Coli ◽  
Nasal Vaccine ◽  
Intranasal Vaccine ◽  
Nasal Immunization

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 andE. coliheat-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.

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 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.

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.

scholarly journals The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced AmyloidβBinding Antibodies on Cynomolgus Monkeys and Guinea Pigs

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Akira Yano ◽  
Kaori Ito ◽  
Yoshikatsu Miwa ◽  
Yoshito Kanazawa ◽  
Akiko Chiba ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Guinea Pigs ◽  
Peptide Vaccine ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Peptide Vaccination ◽  
Binding Profile ◽  
Cynomolgus Monkeys ◽  
The Brain

The reduction of brain amyloid beta (Aβ) peptides by anti-Aβantibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβpeptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβantibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβantibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42compared to Aβfibrils. The levels of serum anti-Aβantibodies and plasma Aβpeptides increased in both animals and decreased the brain Aβ40level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβantibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβpeptides and their toxic effects via clearance of Aβpeptides by generated antibodies.

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