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 Vaccines in Congenital Toxoplasmosis: Advances and Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Mariana Barros ◽  
Daniela Teixeira ◽  
Manuel Vilanova ◽  
Alexandra Correia ◽  
Natercia Teixeira ◽  
...  
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Immune Responses ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Transmitted Infection ◽  
Subunit Vaccines ◽  
Parasitic Burden ◽  
Induced Immunity ◽  
Maternal Fetal Interface

Congenital toxoplasmosis has a high impact on human disease worldwide, inducing serious consequences from fetus to adulthood. Despite this, there are currently no human vaccines available to prevent this infection. Most vaccination studies against Toxoplasma gondii infection used animal models in which the infection was established by exogenous inoculation. Here, we review recent research on potential T. gondii vaccines using animal models in which infection was congenitally established. Endeavors in this field have so far revealed that live or subunit vaccines previously found to confer protection against extrinsically established infections can also protect, at least partially, from vertically transmitted infection. Nevertheless, there is no consensus on the more adequate immune response to protect the host and the fetus in congenital infection. Most of the vaccination studies rely on the assessment of maternal systemic immune responses, quantification of parasitic loads in the fetuses, and survival indexes and/or brain parasitic burden in the neonates. More research must be carried out not only to explore new vaccines but also to further study the nature of the elicited immune protection at the maternal-fetal interface. Particularly, the cellular and molecular effector mechanisms at the maternal-fetal interface induced by immunization remain poorly characterized. Deeper knowledge on the immune response at this specific location will certainly help to refine the vaccine-induced immunity and, consequently, to provide the most effective and safest protection against T. gondii vertical infection.

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 Rational Design and In Vivo Characterization of Vaccine Adjuvants

ILAR Journal ◽  
2018 ◽  
Vol 59 (3) ◽  
pp. 309-322
Author(s):  
Signe Tandrup Schmidt ◽  
Gabriel Kristian Pedersen ◽  
Dennis Christensen
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Rational Design ◽  
Immune Cell ◽  
Whole Body ◽  
Target Antigen ◽  
Vaccine Adjuvants ◽  
Human Situation ◽  
And Function

Abstract Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant mechanism of action and efficacy are usually evaluated in animal models, where mice are by far the most used. In this review, we present methods for assessing adjuvant efficacy and function in animal models: (1) whole-body biodistribution evaluated by using fluorescently and radioactively labeled vaccine components; (2) association and activation of immune cell subsets at the injection site, in the draining lymph node, and the spleen; (4) adaptive immune responses, such as cytotoxic T-lymphocytes, various T-helper cell subsets, and antibody responses, which may be quantitatively evaluated using ELISA, ELISPOT, and immunoplex assays and qualitatively evaluated using flow cytometric and single cell sequencing assays; and (5) effector responses, for example, antigen-specific cytotoxic potential of CD8+ T cells and antibody neutralization assays. While the vaccine-induced immune responses in mice often correlate with the responses induced in humans, there are instances where immune responses detected in mice are not translated to the human situation. We discuss some examples of correlation and discrepancy between mouse and human immune responses and how to understand them.

scholarly journals H9N2 Influenza Whole Inactivated Virus Combined with Polyethyleneimine Strongly Enhances Mucosal and Systemic Immunity after Intranasal Immunization in Mice

2015 ◽  
Vol 22 (4) ◽  
pp. 421-429 ◽  
Author(s):  
Tao Qin ◽  
Yinyan Yin ◽  
Lulu Huang ◽  
Qinghua Yu ◽  
Qian Yang
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Cellular Uptake ◽  
Gene Transfection ◽  
Antibody Responses ◽  
Endosomal Escape ◽  
Adjuvant Activity ◽  
Subunit Vaccines ◽  
Mucosal Delivery

ABSTRACTInfluenza whole inactivated virus (WIV) is more immunogenic and induces protective antibody responses compared with other formulations, like split virus or subunit vaccines, after intranasal mucosal delivery. Polyethyleneimine (PEI), an organic polycation, is widely used as a reagent for gene transfection and DNA vaccine delivery. Although PEI recently has demonstrated potent mucosal adjuvant activity for viral subunit glycoprotein antigens, its immune activity with H9N2 WIV is not well demonstrated. Here, mice were immunized intranasally with H9N2 WIV combined with PEI, and the levels of local respiratory tract and systemic immune responses were measured. Compared to H9N2 WIV alone, antigen-specific IgA levels in the local nasal cavity, trachea, and lung, as well as levels of IgG and its subtypes (IgG1 and IgG2a) in the serum, were strongly enhanced with the combination. Similarly, the activation and proliferation of splenocytes were markedly increased. In addition, PEI is superior as an H9N2 WIV delivery system due to its ability to greatly increase the viral adhesion to mucosal epithelial cells and to enhance the cellular uptake and endosomal escape of antigens in dendritic cells (DCs) and further significantly activate DCs to mature. Taken together, these results provided more insights that PEI has potential as an adjuvant for H9N2 particle antigen intranasal vaccination.

scholarly journals Lipopolysaccharide Derived From the Lymphoid-Resident Commensal Bacteria Alcaligenes faecalis Functions as an Effective Nasal Adjuvant to Augment IgA Antibody and Th17 Cell Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunru Wang ◽  
Koji Hosomi ◽  
Atsushi Shimoyama ◽  
Ken Yoshii ◽  
Takahiro Nagatake ◽  
...  
Keyword(s):  
T Cells ◽  
Alcaligenes Faecalis ◽  
Nasal Administration ◽  
Vaccine Adjuvant ◽  
Adjuvant Activity ◽  
Cervical Lymph Nodes ◽  
Nasal Vaccine ◽  
Benign Nature ◽  
Nasal Immunization ◽  
Follicular T Helper Cells

Alcaligenes spp., including A. faecalis, is a gram-negative facultative bacterium uniquely residing inside the Peyer’s patches. We previously showed that A. faecalis-derived lipopolysaccharides (Alcaligenes LPS) acts as a weak agonist of toll-like receptor 4 to activate dendritic cells and shows adjuvant activity by enhancing IgG and Th17 responses to systemic vaccination. Here, we examined the efficacy of Alcaligenes LPS as a nasal vaccine adjuvant. Nasal immunization with ovalbumin (OVA) plus Alcaligenes LPS induced follicular T helper cells and germinal center formation in the nasopharynx-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs), and consequently enhanced OVA-specific IgA and IgG responses in the respiratory tract and serum. In addition, nasal immunization with OVA plus Alcaligenes LPS induced OVA-specific T cells producing IL-17 and/or IL-10, whereas nasal immunization with OVA plus cholera toxin (CT) induced OVA-specific T cells producing IFN-γ and IL-17, which are recognized as pathogenic type of Th17 cells. In addition, CT, but not Alcaligenes LPS, promoted the production of TNF-α and IL-5 by T cells. Nasal immunization with OVA plus CT, but not Alcaligenes LPS, led to increased numbers of neutrophils and eosinophils in the nasal cavity. Together, these findings indicate that the benign nature of Alcaligenes LPS is an effective nasal vaccine adjuvant that induces antigen-specific mucosal and systemic immune responses without activation of inflammatory cascade after nasal administration.

scholarly journals Recent advances in delivery of veterinary DNA vaccines against avian pathogens

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Seyed Davoud Jazayeri ◽  
Chit Laa Poh
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Dna Vaccines ◽  
Mass Vaccination ◽  
Field Conditions ◽  
Risk Of Infection ◽  
Poultry Industry ◽  
Subunit Vaccines ◽  
Recent Advances ◽  
Multiple Pathogens

Abstract Veterinary vaccines need to have desired characteristics, such as being effective, inexpensive, easy to administer, suitable for mass vaccination and stable under field conditions. DNA vaccines have been proposed as potential solutions for poultry diseases since they are subunit vaccines with no risk of infection or reversion to virulence. DNA vaccines can be utilized for simultaneous immunizations against multiple pathogens and are relatively easy to design and inexpensive to manufacture and store. Administration of DNA vaccines has been shown to stimulate immune responses and provide protection from challenges in different animal models. Although DNA vaccines offer advantages, setbacks including the inability to induce strong immunity, and the fact that they are not currently applicable for mass vaccination impede the use of DNA vaccines in the poultry industry. The use of either biological or physical carriers has been proposed as a solution to overcome the current delivery limitations of DNA vaccines for veterinary applications. This review presents an overview of the recent development of carriers for delivery of veterinary DNA vaccines against avian pathogens.

scholarly journals Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens

2021 ◽  
Vol 12 ◽  
Author(s):  
Brandi T. Johnson-Weaver ◽  
Hae Woong Choi ◽  
Hang Yang ◽  
Josh A. Granek ◽  
Cliburn Chan ◽  
...  
Keyword(s):  
Mast Cell ◽  
West Nile Virus ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvants ◽  
West Nile ◽  
Adjuvant Activity ◽  
Nasal Vaccine

Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. However, small molecule mast cell activators may be a more cost-efficient adjuvant alternative that is easily synthesized with high purity compared to M7 or C48/80. To identify novel mast cell activating compounds that could be evaluated for mucosal vaccine adjuvant activity, we employed high-throughput screening to assess over 55,000 small molecules for mast cell degranulation activity. Fifteen mast cell activating compounds were down-selected to five compounds based on in vitro immune activation activities including cytokine production and cellular cytotoxicity, synthesis feasibility, and selection for functional diversity. These small molecule mast cell activators were evaluated for in vivo adjuvant activity and induction of protective immunity against West Nile Virus infection in BALB/c mice when combined with West Nile Virus envelope domain III (EDIII) protein in a nasal vaccine. We found that three of the five mast cell activators, ST101036, ST048871, and R529877, evoked high levels of EDIII-specific antibody and conferred comparable levels of protection against WNV challenge. The level of protection provided by these small molecule mast cell activators was comparable to the protection evoked by M7 (67%) but markedly higher than the levels seen with mice immunized with EDIII alone (no adjuvant 33%). Thus, novel small molecule mast cell activators identified by high throughput screening are as efficacious as previously described mast cell activators when used as nasal vaccine adjuvants and represent next-generation mast cell activators for evaluation in mucosal vaccine studies.

scholarly journals A De-O-acylated Lipooligosaccharide-Based Adjuvant System Promotes Antibody and Th1-Type Immune Responses to H1N1 Pandemic Influenza Vaccine in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Ji In Ryu ◽  
Shin Ae Park ◽  
Seo Ri Wui ◽  
Ara Ko ◽  
Ji Eun Han ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Pandemic Influenza ◽  
Inflammatory Responses ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
H1n1 Pandemic ◽  
Vaccine Adjuvants ◽  
Adjuvant Activity ◽  
Adjuvant System

Vaccine adjuvants are agents that are used to promote immune responses to vaccine antigens and thereby to enhance the protective efficacy of the vaccines. In this study, we investigated the adjuvant activity of CIA06, an adjuvant system that is composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS) and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu-S® in mice. CIA06 significantly enhanced influenza-specific serum IgG, hemagglutination-inhibition, and virus-neutralizing antibody titers, which eliminated vaccine dose-dependency in the antibody response. Mice immunized with the CIA06-adjuvanted Greenflu-S showed Th1-type-predominant cytokine profiles, and both CD4+and CD8+T cell responses were induced. Immunization of mice with the CIA06-adjuvanted vaccine reduced the mortality and morbidity of mice upon lethal challenges with influenza virus, and no excessive inflammatory responses were observed in the lung tissues of the immunized mice after viral infection. These data suggest that the dLOS-based adjuvant system CIA06 can be used to promote the immune responses to influenza vaccine or to spare antigen dose without causing harmful inflammatory responses.

scholarly journals Polyphosphazenes as Adjuvants for Animal Vaccines and Other Medical Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Dylan J. Chand ◽  
Royford B. Magiri ◽  
Heather L. Wilson ◽  
George K. Mutwiri
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Animal Species ◽  
Mechanisms Of Action ◽  
Present Review ◽  
Medical Applications ◽  
Large Animal ◽  
Vaccine Adjuvants ◽  
Adjuvant Activity ◽  
Laboratory Rodents

Polyphosphazenes are a class of experimental adjuvants that have shown great versatility as vaccine adjuvants in many animal species ranging from laboratory rodents to large animal species. Their adjuvant activity has shown promising results with numerous viral and bacterial antigens, as well as with crude and purified antigens. Vaccines adjuvanted with polyphosphazenes can be delivered via systemic and mucosal administration including respiratory, oral, rectal, and intravaginal routes. Polyphosphazenes can be used in combination with other adjuvants, further enhancing immune responses to antigens. The mechanisms of action of polyphosphazenes have not fully been defined, but several systematic studies have suggested that they act primarily by activating innate immunity. In the present review, we will highlight progress in the development of polyphosphazenes as adjuvants in animals and their other medical applications.

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