Modern peptide and protein subunit vaccines suffer from poor immunogenicity and require the use of adjuvants. However, none of the currently licensed adjuvants can elicit cell-mediated immunity or are suitable for mucosal immunization. In this study we explored the immunological effect of nasal co-administration of adjuvants with distinct functions: cholera toxin subunit B, a potent mucosal adjuvant that induces strong humoral responses, muramy di-peptide (MDP), an adjuvant known to elicit cell mediated immunity but rarely used nasally, and chitosan, an adjuvant that achieves specific physiological effects on mucosal membranes that improve antigen uptake. Groups of five female BALB/c mice received on days 1 and 56 nasal instillations of the recombinant Helicobacter pylori antigen urease admixed to single or multiple adjuvant combinations. Serum IgG kinetics were followed over 24 weeks. At the conclusion of the experiment, local antibody responses were determined and antigen-specific recall responses in splenocyte cultures were assayed for proliferation and cytokine production. The combination of adjuvants was shown to further contribute to the increased antigenicity of recombinant H. pylori urease. The data presented here outline and support facilitation of increased immunomodulation by an adjuvant previously defined as an effective mucosal adjuvant (chitosan) for another adjuvant (MDP) that is not normally effective via this route.
: Around the world, approximately 5 million people became infected with HIV in 2001, an estimated 70% via sexual transmission. Numerous studies have demonstrated that it is difficult to achieve total protection from vaginally or rectally acquired HIV/SIV when using parenteral immunization. Mucosal immunization was seen as the best approach to achieve sustainable immune responses at mucosal sites of viral entry. This was further emphasized when several studies implicated rectal and vaginal mucosa...
#1Kenneth C. Bagley(UMBI: University of Maryland Biotechnology Institute)H-Index: 10
#2Sayed F. Abdelwahab(UMBI: University of Maryland Biotechnology Institute)H-Index: 19
Last. George K. Lewis(UMBI: University of Maryland Biotechnology Institute)H-Index: 60
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The cholera-like enterotoxins (CLETS), cholera toxin (CT) and Escherichia coli heat-labile toxin (LT), are powerful mucosal adjuvants. Here we show that these toxins also induce a long-lived blockade (of at least 6 months) on the induction of oral tolerance when they are coadministered with the antigen ovalbumin. Strikingly, only enzymatically active CLETS induced this blockade on the induction of oral tolerance. In this regard, the enzymatically inactive mutants of CT and LT, CTK63 and LTK63, a...
The potentiation of immune responses to tumor-associated antigen (Ag) is a pivotal issue in immunotherapy for cancer and thus requires the use of adjuvants, which are involved in efficient antibody (Ab) production and killer cell induction. The efficacy for tumor regression of a number of adjuvants that have been applied to immunotherapy in humans and tumor-bearing animal models has been tested without understanding of the function of adjuvants. Recent findings on the function of Toll-like recep...
Mucosal antigen encounter usually results in a state of systemic non-responsiveness (tolerance). This failure to mount a protective response is a major hurdle to mucosal vaccine development. Hence, the identification of safe and effective mucosal adjuvants promoting protective immunity is of critical importance. The non-toxic B subunit of Escherichia coli heat labile enterotoxin(EtxB) is a potent nasal adjuvant; however, its usefulness following oral delivery is unconfirmed. We used DO11.10 chim...
In this paper we evaluated chitosan microparticles as a vaccine delivery system as well as the mucosal adjuvant LTK63, a nontoxic Escherichia coli enterotoxin (LT) mutant for the intranasal immunization with the group C meningococcal conjugated vaccine (CRM-MenC). Mice receiving intranasally the CRM-MenC vaccine formulated with chitosan microparticles and the LTK63 mutant showed higher titers of systemic and mucosal antibodies specific for the group C meningococcal polysaccharide as compared to ...
#1Yan Zhang(WSU: Washington State University)H-Index: 2
#2Guy H. Palmer(WSU: Washington State University)H-Index: 70
Last. Wendy C. Brown(WSU: Washington State University)H-Index: 61
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Abstract Immunostimulatory oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) stimulate IL-12-dependent Th1 dominated cytokine and enhanced IgG responses when co-delivered with antigen to mice. However, the CpG ODN sequences that are optimal for each mammalian species may differ. Previously, we demonstrated that a CpG ODN containing the GTCGTT motif was optimal for stimulating bovine B cell proliferation, and induced IL-6, IL-12 and IFN-γ production by peripheral blood mon...
Last. Ali Mharandi(University of Gothenburg)H-Index: 1
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Mucosal immunisation may be used both to prevent mucosal infections through the activation of anti-microbial immunity and to treat selected autoimmune, allergic or infectious-immunopathological disorders through the induction of antigen-specific tolerance. The development of mucosal vaccines, whether for prevention of infectious diseases or for immunotherapy, requires antigen delivery and adjuvant systems that can efficiently help to present vaccine or immunotherapy antigens to the mucosal immun...
Abstract Interleukin-12 (IL-12) is a heterodimeric cytokine that enhances immune responses to bacterial, parasitic, and viral pathogens, and leads to tumor regression in animal models. For this reason, the use of IL-12 as a vaccine adjuvant and as a therapeutic agent for the treatment of cancer is being investigated. Unfortunately, the extreme toxicity of this molecule observed during clinical trials has limited its use. This toxicity correlates with increased IFN-γ expression, decreased glucose...
Modern subunit vaccines are composed of antigens and a delivery system and/or adjuvant (immune stimulator) that triggers the desired immune responses. Adjuvants mimic pathogen-associated molecular patterns (PAMPs) that are typically associated with infections. Carbohydrates displayed on the surface of pathogens are often recognized as PAMPs by receptors on antigen-presenting cells (APCs). Consequently, carbohydrates and their analogues have been used as adjuvants and delivery systems to promote ...
Last. Istvan Toth(UQ: University of Queensland)H-Index: 61
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Innate immune system plays an important role in pathogen detection and the recognition of vaccines, mainly through pattern recognition receptors (PRRs) that identify pathogen components (danger signals). One of the typically recognised bacterial components are lipids in conjugation with peptides, proteins and saccharides. Lipidic compounds are readily recognised by the immune system, and thus are ideal candidates for peptide-based vaccine delivery. Thus, bacterial or synthetic lipids mixed with,...
Abstract The high global burden of tuberculosis (TB) underscores the urgent need for an effective TB vaccine since the only licensed Bacillus Calmette-Guerin (BCG) vaccine is ineffective in preventing adult pulmonary TB and affords no protection against latent TB infection (LTBI). Herein we investigated the potential of Mycobacterium tuberculosis ( Mtb ) antigen proteins AEC comprised of Ag85b and ESAT6-CFP10 proteins in conjunction with aluminum (Al) and polyriboinosinic-polyribocytidylic acid ...
#1Yoshifumi Naito(Kyoto Prefectural University of Medicine)H-Index: 9
#2Saeko Hamaoka(Kyoto Prefectural University of Medicine)H-Index: 8
Last. Teiji Sawa(Kyoto Prefectural University of Medicine)H-Index: 35
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: An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it can cause. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven groups of mice w...
ABSTRACTMetal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe2O4 NPs were...
Herein we describe a formulation of self-encapsulating poly(lactic-co-glycolic acid) (PLGA) microspheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into premade PLGA microspheres. Calcium phosphate (CaHPO4) adjuvant gel was incorporated into the microspheres as a protein-trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 ± 0.31 ...
Abstract Our group has developed a subunit vaccine candidate against Dengue virus (DENV) based on two different viral regions, the domain III of the envelope protein and the capsid protein. The chimeric proteins for each serotype (DIIIC1-4), aggregated with the oligodeoxynucleotide 39 M, form the tetravalent formulation named Tetra DIIIC. Tetra DIIIC induces a protective immune response in mice when it is inoculated by intraperitoneal route. However, if children are the main targets for a DENV v...
The upper respiratory tract (URT) is the major entry site for human pathogens and strategies to activate this network could lead to new vaccines capable of preventing infection with many pathogens. Group A streptococcus (GAS) infections, causing rheumatic fever, rheumatic heart disease, and invasive disease, are responsible for substantial morbidity and mortality. We describe an innovative vaccine strategy to induce mucosal antibodies of significant magnitude against peptide antigens of GAS usin...
Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action...
Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action...
