Search PubMed⌕ Search

Biomedical subjects

Harm HogenEsch

Publications and source records attributed to Harm HogenEsch.

At least 19 recordsLinked to original sources
PubMed2006

Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants.

The degree of antigen adsorption by aluminum-containing adjuvants is considered an important characteristic of vaccines that is related to immunopotentiation by the adjuvant. This study examined immunopotentiation by aluminum phosphate adjuvant in three model vaccines in which the antigen was not adsorbed in the vaccine formulation nor when mixed in vitro with interstitial fluid. In the first model vaccine, aluminum phosphate adjuvant was pre-treated with 0.5 M KH2PO4 to minimize the adsorption of dephosphorylated alpha casein. The second model vaccine was composed of aluminum phosphate adjuvant and ovalbumin that was dephosphorylated by treatment with potato acid phosphatase. The third model vaccine consisted of aluminum phosphate adjuvant and lysozyme (LYS). In order to prevent adsorption of lysozyme, the aluminum phosphate adjuvant was pre-treated with fibrinogen, a protein present in interstitial fluid that binds strongly to aluminum phosphate adjuvant. Immunopotentiation was evaluated by measuring antibody production in mice. It was found that all three model vaccines induced antibody titers that were statistically higher than induced by a solution of antigen without adjuvant and similar to vaccines in which the antigens were adsorbed by aluminum phosphate adjuvant. Confocal microscopy experiments suggested that the antigens used in these experiments, even though not adsorbed to the aluminum phosphate adjuvant, were trapped in void spaces within the adjuvant aggregates, resulting in uptake of antigen by dendritic cells.

Adjuvants, Immunologic↗
PubMed2006

Cytokine expression in normal and inflamed esophageal mucosa: a study into the pathogenesis of allergic eosinophilic esophagitis.

OBJECTIVES: We studied the expression of cytokines and inflammatory cells in normal and inflamed esophageal mucosa of children with the aim of furthering our understanding of the pathophysiology of allergic eosinophilic esophagitis (AEE). METHODS: Controls and AEE patients (>or=15 eosinophils/high-power field on esophageal mucosal biopsies) between the ages of 1 and 18 years were recruited. Esophageal biopsies were obtained for histologic examination, immunohistochemical studies, and cytokine analysis. RESULTS: Eight controls (4 males; mean age 9.99 years) and 11 AEE patients (8 males; mean age 7.15 years) were studied. mRNA expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-5, IL-13, eotaxin-1, eotaxin-2, eotaxin-3, and RANTES was studied. IFN-gamma and IL-5 expressions were significantly up-regulated in AEE patients compared with controls. Expressions of IL-4 and IL-13 were similar between AEE patients and controls. Eotaxin-1 expression was significantly up-regulated in AEE patients, whereas eotaxin-2 was up-regulated in controls. Expression of RANTES and eotaxin-3 was similar between the two groups. There was increased staining for mast cells in AEE patients compared with controls. CONCLUSIONS: Our data suggests that AEE is primarily an IL-5 selective TH2 response, with a possible TH1 component, and a differential role of eosinophilic chemoattractants. The role of mast cells in the pathogenesis of AEE needs additional study.

Adolescent↗
PubMed2006

Expression of chitinase-like proteins in the skin of chronic proliferative dermatitis (cpdm/cpdm) mice.

Mammalian chitinase-like proteins belong to a family of proteins structurally related to chitinases but devoid of enzymatic activity. They have a postulated role in remodeling of extracellular matrix and defense mechanisms against chitin-containing pathogens. The expression of these proteins is increased in parasitic infections and allergic airway disease, but their expression in dermatitis has not been examined. The mRNA expression of two chitinase 3-like (Chi3L) proteins, Chi3L3 (Ym1) and Chi3L4 (Ym2), was determined in the skin of normal mice, chronic proliferative dermatitis (cpdm/cpdm) mutant mice and mice with experimentally induced contact hypersensitivity reaction. The localization of Chi3L3 and Chi3L4 proteins in cells was determined by fluorescence microscopy of double-labeled frozen sections of skin, and confirmed in vitro by stimulation of macrophages and mast cells with cytokines. Quantitative RT-PCR demonstrated a 976-fold increase of Chi3l4 mRNA expression and a 24-fold increase of Chi3l3 mRNA expression in the skin of cpdm/cpdm mice. Their expression was also increased in the ears of mice with 2,4-dinitrofluorobenzene-induced contact hypersensitivity, but the increase was greater for Chi3l3 mRNA (51-fold) than Chi3l4 mRNA (32-fold). Western blot analysis with an antibody against Chi3L3 and Chi3L4 confirmed the increased amount of these proteins in the skin of cpdm/cpdm mice. Two-color immunofluorescence identified macrophages, dendritic cells and mast cells as cellular sources of Chi3L3 and Chi3L4 proteins. Eosinophils and neutrophils did not contain detectable concentrations of these proteins. Treatment of macrophages and mast cells in vitro with interleukin-4 induced expression of Chi3l3 and Chi3l4 mRNA.

Animals↗
PubMed2005

Porcine circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice.

BACKGROUND: We have previously described microscopic and electron microscopic alterations in lymphoid organs of PCV2 inoculated mice as apoptosis. In this study we wanted to investigate the molecular pathogenetic mechanism of PCV2-induced apoptosis. Eight-week old BALB/c mice were either sham inoculated (control mice) or inoculated intraperitoneally (ip) and intranasally (in) with a single (sPCV mice) or multiple (mPCV mice) doses of PCV2. Four control mice and 4 sPCV mice were sacrificed 7, 14, 28 and 42 days post inoculation (PI). All 4 mPCV mice were sacrificed 42 days PI. Following necropsy, immunohistochemistry for caspase 3 and in-situ TUNEL assay were performed on sections of spleen, lymph nodes, thymus and ileum from control, sPCV and mPCV mice. In addition, total RNA was extracted from spleens of control, sPCV and mPCV mice for simultaneous detection and semiquantitation of bcl-2 homologues and various caspase mRNAs using a multiprobe RNase protection assay system. RESULTS: PCV2 replicated and was associated with apoptosis in spleens, lymph nodes and Peyer's patches of infected BALB/c mice. Upregulation of caspase 1, 2, 3, 6, 7, 8, 11 and 12 and upregulation for the transcripts of apoptosis inhibitors bcl-2, bcl-w and bcl-X and apoptosis promoters' bax, bak and bad was detected in spleens of sPCV and mPCV mice, but not control mice. Apoptosis was further confirmed by light and electron microscopic morphology as well as by positive TUNEL assay and detection of activated caspase 3. PCV2 nucleic acid was detected by in-situ hybridization in the nuclei and cytoplasm of such apoptotic cells. CONCLUSION: The data presented here support the hypothesis that PCV2 induces apoptosis mediated through the activation of caspases 8 and 3 in the spleens of infected mice.

Journal Article↗
PubMed2005

Relationship of adsorption mechanism of antigens by aluminum-containing adjuvants to in vitro elution in interstitial fluid.

The objective of this research was to determine how the mechanism by which antigens adsorb to aluminum-containing adjuvants affects the elution upon exposure to interstitial fluid. Antigens (alpha lactalbumin, bovine serum albumin, lysozyme and myoglobin) that adsorb to aluminum-containing adjuvants principally by electrostatic attraction were found to elute readily in vitro when exposed to interstitial fluid. Phosphorylated antigens (alpha casein, hepatitis B surface antigen and phosphorylated bovine serum albumin) that adsorb to aluminum-containing adjuvants principally by ligand exchange exhibit little if any elution during 12-24 h in vitro exposure to interstitial fluid. Dephosphorylated alpha casein, which contains less than two phosphate groups, was less strongly adsorbed by ligand exchange in comparison to alpha casein, which contains eight phosphate groups. Dephosphorylated alpha casein was completely eluted when exposed to interstitial fluid. The results of this study lead to the generalization that antigens that adsorb to aluminum-containing adjuvants by electrostatic attraction are more likely to elute upon intramuscular or subcutaneous administration than antigens that adsorb by ligand exchange.

Adjuvants, Immunologic↗
PubMed2005

Genes upregulated in a metastasizing human colon carcinoma cell line.

Differential gene expression between the metastatic human colon cancer cell line HT29p and its nonmetastatic counterpart HT29-MTX was revealed by suppression subtractive hybridization. Fifty-eight individual genes showed increased mRNA levels in HT29p cells. Only 15 of these genes had been related to transformation in previous studies; the majority of genes are new candidates encoding proteins relevant for the metastatic process. Cancer profiling arrays as well as in situ hybridization study revealed that at least some of the genes obtained in the SSH screen are also differentially expressed in human tumors.

Animals↗
PubMed2005

Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro.

An important step in the induction of an immune response to vaccines is the internalization of antigens by antigen presenting cells, such as dendritic cells (DCs). Many current vaccines are formulated with antigens adsorbed to an aluminum-containing adjuvant. Following injection of the vaccine the antigens may either elute or stay adsorbed to the adjuvant surface. Antigens, which elute from the adjuvant surface, are internalized by dendritic cells through macropinocytosis while those that remain adsorbed are internalized with the adjuvant particle by phagocytosis. The relative efficiency of these two routes of internalization was studied. Alpha casein (AC) labeled with a green fluorescent dye was selected as the model antigen. In order to model vaccine antigens that elute from aluminum-containing adjuvants following administration, dendritic cells were incubated with a solution of fluorochrome-labeled alpha casein. To model vaccine antigens that do not elute from aluminum-containing adjuvants following administration, dendritic cells were exposed to fluorochrome-labeled alpha casein adsorbed to aluminum hydroxide adjuvant (AH). Alpha casein has eight phosphate groups and adsorbs to aluminum hydroxide adjuvant through ligand exchange. Alpha casein does not elute from aluminum hydroxide adjuvant upon exposure to cell culture media. The uptake of antigen by dendritic cells was determined at 0.5, 1, 2 and 3h by confocal microscopy and flow cytometry. Dendritic cells internalized both alpha casein in solution and alpha casein adsorbed to aluminum hydroxide adjuvant. However, the mean fluorescence intensity of dendritic cells incubated with adsorbed alpha casein was four times greater than dendritic cells incubated with alpha casein in solution. In addition, the internalization of alpha casein was enhanced when the mean aggregate diameter of the adjuvant in the cell culture media was reduced from 17 microm to 3 microm. It was concluded that antigen internalization by dendritic cells was enhanced when the antigen remained adsorbed to the aluminum-containing adjuvant following administration and the aggregate size of the adjuvant was smaller than dendritic cells which are approximately 10 microm in diameter.

Adjuvants, Immunologic↗
PubMed2005

Increased expression of chemokines in the skin of chronic proliferative dermatitis mutant mice.

Chemokines direct the migration of leukocytes to sites of inflammation and are potential targets for anti-inflammatory therapy. Chronic proliferative dermatitis (cpdm/cpdm) mutant mice develop a persistent eosinophilic dermatitis associated with increased T(H)2 cytokines in the skin. Expression patterns of chemokines in the skin of cpdm/cpdm mice were evaluated to define the mechanisms driving cutaneous infiltration by leukocytes. RNA isolated from the skin of mutant and littermate control mice revealed a significant increase in Ccl1 (TCA-3), Ccl2 (MCP-1), Ccl11 (eotaxin), Ccl17 (TARC), Cxcl10 (IP-10), and the chemokine receptor Ccr3. The concentration of CCL11 protein was increased two- to threefold in the skin of cpdm/cpdm mice by enzyme-linked immunosorbent assay. In vitro culture of primary dermal fibroblasts from cpdm/cpdm and control mice with tumor necrosis factor, IL-4, and IL-13 stimulation did not reveal differences in their ability to secrete CCL11, suggesting that the increased chemokine expression observed in the skin of cpdm/cpdm mice is most likely caused by the increased T(H)2 cytokines in the dermis of this mouse model. Treatment of cpdm/cpdm mice with CCL11-neutralizing polyclonal antibodies did not affect the number of eosinophils in the skin or the severity of the dermatitis. Neutralizing multiple chemokines or chemokine receptors may be necessary to decrease eosinophil accumulation. The cpdm/cpdm mutant mouse is a potentially useful model to determine the role of various chemokines in eosinophil accumulation in chronic inflammation.

Animals↗
PubMed2004

Distribution of adsorbed antigen in mono-valent and combination vaccines.

The distribution of alpha-casein, bovine serum albumin (BSA), myoglobin and recombinant protective antigen (rPA) in mono-valent and combination vaccines containing aluminum hydroxide adjuvant was studied by fluorescence microscopy and flow cytometry. Green and red fluorescent probes were conjugated to the antigens. Adsorption isotherms of the fluorescently labeled proteins to aluminum hydroxide adjuvant demonstrated that incorporation of the fluorescent probe did not significantly affect the adsorption. In mono-valent vaccine systems, antigen adsorption occurred within one minute and uniform surface coverage of the adjuvant aggregates was observed within 1h. Content uniformity was achieved through a cycle of de-aggregation and re-aggregation of the aluminum hydroxide adjuvant aggregates caused by mixing. For combination vaccines, two antigens were adsorbed separately to the aluminum hydroxide adjuvant prior to combination. Following combination, cycles of de-aggregation and re-aggregation occurred due to mixing, which led to uniform distribution of both antigens. The results of this study indicate that content uniformity should not be an issue during the production of mono-valent or combination vaccines as long as adequate mixing procedures are followed.

Absorption↗
PubMed2004

Mechanism of adsorption of hepatitis B surface antigen by aluminum hydroxide adjuvant.

Hepatitis B surface antigen (HBsAg) differs from many antigens because of its associated lipid bilayer that is largely composed of phospholipids. In general, phosphate groups adsorb strongly to hydroxylated mineral surfaces by ligand exchange. The purpose of this study was to investigate the mechanism of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant with emphasis on the role of phospholipids in this adsorption. The adsorption of HBsAg by aluminum hydroxide adjuvant exhibits a high affinity adsorption isotherm. The Langmuir equation was used to calculate the adsorptive capacity (1.7 microg/microg Al), which is the amount of HBsAg adsorbed at monolayer coverage and the adsorptive coefficient (6.0 ml/microg), which is a measure of the strength of the adsorption force. The relatively high value of the adsorptive coefficient indicates that adsorption is due to a strong attractive force. Ligand exchange between a phosphate of the antigen and a surface hydroxyl of the adjuvant provides the strongest adsorption mechanism. The adsorption capacity of HBsAg was not affected by increased ionic strength indicating that electrostatic attraction is not the predominant adsorption force. Adsorption was also not affected by the addition of ethylene glycol indicating that hydrophobic interactions were not the predominant adsorption force. The strength of the adsorption force was indicated by the resistance of HBsAg to elution when exposed to interstitial fluid. Less than 5% of the HBsAg adsorbed to aluminum hydroxide adjuvant in a model vaccine was eluted during a 12 h in vitro exposure to interstitial fluid at 37 degrees C. Less than 1% of the adsorbed HBsAg in two commercial vaccines was eluted by in vitro exposure to interstitial fluid for 48 h at 37 degrees C. Thus, it was concluded that adsorption of HBsAg by aluminum hydroxide adjuvant is predominantly due to ligand exchange between the phospholipids in HBsAg and surface hydroxyls in aluminum hydroxide adjuvant.

Adjuvants, Immunologic↗
PubMed2004

Effect of age on immune parameters and the immune response of dogs to vaccines: a cross-sectional study.

The evaluation of anti-aging intervention strategies in dogs would benefit from reliable quantitative biomarkers of aging. In the present study, the expression of various immune parameters was measured in young and old dogs to identify potential biomarkers of aging. The second goal of the study was to determine the effect of age on the immune response to vaccines. The immune function, including the antibody response to vaccines, was determined in 32 young adult (3.15+/-0.8 years of age) and 33 old dogs (12.1+/-1.3 years of age) of various breeds. Old dogs had a significantly lower lymphocyte proliferative response and a lower percentage of CD4+ T cells and CD45R+/CD4+ T cells, and a higher percentage of CD8+ T cells and a higher concentration of serum and salivary IgA. The most significant differences (P<0.001) occurred in the lymphocyte proliferative responses to ConA and PHA, the CD4:CD8 ratio, and the percentage of CD45R+/CD4+ T cells suggesting that these parameters are potential biomarkers of aging. There was no difference in the percentage of total T and B lymphocytes and the concentration of serum IgM and IgG. Both groups of dogs had protective titers against distemper virus, parvovirus and rabies virus before annual revaccination. The pre-vaccination titer against rabies virus was higher in the old dogs than in the young dogs, and there were no differences in post-vaccination titers against any of the viruses. This suggests that annual vaccination protocols provide adequate protection for old dogs.

Age Factors↗
PubMed2003

Relationship between the degree of antigen adsorption to aluminum hydroxide adjuvant in interstitial fluid and antibody production.

The effect of the degree of adsorption after exposure to interstitial fluid on the immune response in mice to model vaccines containing ovalbumin, alpha casein or dephosphorylated alpha casein adsorbed to aluminum hydroxide adjuvant was studied. Ovalbumin and dephosphorylated alpha casein were adsorbed in the vaccine but were completely eluted when exposed to interstitial fluid for 4 h. The presence of aluminum hydroxide adjuvant in the vaccine produced immunopotentiation compared to a solution of the protein even though the protein desorbed rapidly upon subcutaneous administration. In contrast, alpha casein was completely adsorbed to aluminum hydroxide adjuvant in both the vaccine and upon exposure to interstitial fluid. Immunopotentiation by aluminum hydroxide adjuvant was also observed in this model vaccine compared to a solution of alpha casein. The results indicated that antigen presenting cells can take up desorbed antigen from interstitial fluid as well as antigen adsorbed to aluminum-containing adjuvants.

Adjuvants, Immunologic↗
PubMed2003

Effect of the degree of phosphate substitution in aluminum hydroxide adjuvant on the adsorption of phosphorylated proteins.

Aluminum hydroxide adjuvant was pretreated with six concentrations of potassium dihydrogen phosphate to produce a series of adjuvants with various degrees of phosphate substitution for surface hydroxyl. The adsorption of three phosphorylated proteins (alpha casein, dephosphorylated alpha casein, and ovalbumin) by the phosphate-treated aluminum hydroxide adjuvants was studied. The phosphorylated proteins were adsorbed by ligand exchange of phosphate for hydroxyl even when an electrostatic repulsive force was present. However, the extent (adsorptive capacity) and strength (adsorptive coefficient) of adsorption was inversely related to the degree of phosphate substitution of the aluminum hydroxide adjuvant. Exposure of vaccines containing aluminum hydroxide adjuvant and phosphorylated antigens to phosphate ion in the formulation or during manufacture should be minimized to produce maximum adsorption of the antigen.

Adjuvants, Pharmaceutic↗
PubMed2002

Immunization of rabbits against a bacterial pathogen with an alginate microparticle vaccine.

Pasteurella multocida is an important bacterial pathogen of domestic rabbits. To evaluate the ability of a thiocyanate extract (PTE) of P. multocida to stimulate an immune response and protect against infection with P. multocida, rabbits were immunized subcutaneously or intranasally on Days 7, 21 and 35. Cholera toxin, a potent mucosal adjuvant, was included in one treatment group. Rabbits immunized subcutaneously (SC) or intranasally (IN) had significant increases in serum anti-PTE IgG but not IgA. In contrast, only rabbits immunized IN with PTE developed significant titers of nasal lavage anti-PTE IgA and cholera toxin significantly enhanced this response. In a second study rabbits were immunized via the drinking water with PTE incorporated into alginate microparticles on Days 7, 14 and 21. Mild increases in serum IgG were noted in rabbits immunized with PTE in microparticles, with or without cholera toxin, and this increase was significant (P<or=0.05) on Day 21 for rabbits receiving PTE and cholera toxin. Nasal lavage anti-PTE IgA was significantly (P<or=0.05) increased in rabbits immunized orally with PTE, with or without cholera toxin, in microparticles. This effect was not enhanced by cholera toxin. Rabbits orally immunized with PTE in microparticles had significantly fewer colony forming units of homologous P. multocida recovered from the lungs and nasopharynx following an intranasal challenge. These results demonstrate that PTE incorporated into alginate microparticles and administered orally is immunogenic and confers protective immunity.

Alginates↗
PubMed2002

Effects of cellulose derivatives and poly(ethylene oxide)-poly(propylene oxide) tri-block copolymers (Pluronic)surfactants) on the properties of alginate based microspheres and their interactions with phagocytic cells.

The goal of this study was to examine the phagocytosis of alginate based microspheres with different surface properties. Favorable interaction with macrophages is critical for uptake subsequent processing of the microspheres used for oral vaccine delivery. We examined the effects of size of alginate microspheres and hydrophobicity on cellular uptake. We also examined the toxicity of formulation components to phagocytic cells. Alginate microspheres were made by the emulsion-cross-linking technique. Five different formulations of microspheres were evaluated for size, hydrophobicity, cellular uptake and toxicity to macrophages. The formulations examined were: alginate alone (A), alginate with methylcellulose (AA) AA with Pluronic L61 (AA61), alginate with hydroxypropyl methylcellulose (AK3), and AK3 with Pluronic (L61 (AK3 61). Microspheres with without poly-L-lysine (PLL) coating were tested. The mean volume sizes of A, AA, AA61, AK3, AK3 61 microspheres (MS) were 11, 10.5, 3.8, 8.7 and 3.9 mocrom, respectively. After coating them with PLL the mean volume sizes were 10.4, 10, 3.7, 8.8 and 3.5 microm, respectively. Hydrophobicity of the microspheres was evaluated by measuring contact angle on a glass slide coated with the microspheres. The contact angles measured using a goniometer on A, AA, AA61, AK3, AK3 61 MS were 20, 34.8, 71, 29 and 80 degrees, respectively whereas those MS coated with PLL were 49.7, 55.8, 91, 48.25 and 84.4 degrees, respectively. Cellular uptake studies using flow cytometery revealed that AA61 MS coated with PLL were phagocytosed most often by mouse macrophages. There was no statistically significant difference in cellular uptake among those MS without PLL coating. Toxicity to macrophages was shown to depend on the ratio of microspheres to cells. These studies suggest that formulation can dramatically affect the physical characteristics of alginate MS in ways that can affect how they will interact with cells in the body when administered as a vaccine delivery system.

Alginates↗
PubMed2002

Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs.

OBJECTIVE: To determine whether routine vaccination induces antibodies against bovine thyroglobulin and autoantibodies against canine thyroglobulin in dogs. DESIGN: Prospective study. ANIMALS: 20 healthy research Beagles and 16 healthy pet dogs. PROCEDURE: For the research Beagles, 5 dogs were vaccinated with a multivalent vaccine and a rabies vaccine, 5 dogs received only the multivalent vaccine, 5 dogs received only the rabies vaccine, and 5 dogs were unvaccinated controls. The multivalent vaccine was administered at 8, 10, 12, 16, 20, 26, and 52 weeks of age and every 6 months thereafter. The rabies vaccine was administered at 16 and 52 weeks of age and then once per year. Blood was collected from all dogs at 8, 16, and 26 weeks of age and then 4 times yearly. Assays for antibodies directed against bovine and canine thyroglobulin were performed prior to and 2 weeks after each yearly vaccination. For the pet dogs, blood was collected prior to and 2 weeks after 1 vaccination. RESULTS: In the research Beagles, there was a significant increase in anti-bovine thyroglobulin antibodies in all vaccinated dogs, compared with control dogs. There was a significant increase in anti-canine thyroglobulin antibodies in the 2 groups of dogs that received the rabies vaccine but not in the group that received the multivalent vaccine alone. In the pet dogs, there was a significant increase in anti-canine thyroglobulin antibodies after vaccination but no significant change in anti-bovine thyroglobulin antibodies. CONCLUSIONS AND CLINICAL RELEVANCE: Recent vaccination may result in increased anti-canine thyroglobulin antibodies. Whether these antibodies have a deleterious effect on canine thyroid function is unknown.

Animals↗
PubMed2002

Mechanisms of stimulation of the immune response by aluminum adjuvants.

Aluminum adjuvants are widely used in human and veterinary vaccines. They are appropriate adjuvants for vaccines that confer protection by inducing antibodies via the induction of a type 2 immune response, but they do not induce cytotoxic T cell and cell-mediated immunity. The mechanisms by which aluminum adjuvants selectively enhance the immune response are poorly understood. Following exposure to interstitial fluid in vitro and in vivo, most antigens are rapidly desorbed from aluminum adjuvants, suggesting that sustained release of antigen from a depot does not significantly contribute to the adjuvant effect of aluminum compounds. However, the adsorption of antigens onto aluminum salts may result in a high local concentration of antigen at the injection site and enhance the uptake by antigen-presenting cells. Aluminum compounds can further enhance the immune response by direct or indirect stimulation of dendritic cells, activation of complement and by inducing the release of chemokines. The relative importance of these mechanisms remains to be determined.

Adjuvants, Immunologic↗