Calcium-phosphate-adjuvanted allergens: Total and specific IgE levels before and after immunotherapy with house dust and Dermatophagoides pteronyssinus extracts

Ickovic, M. R.; Relyveld, E. H.; Hénocq, E; David, B.; Marie, F.-N.

doi:10.1016/s0769-2625(83)80029-4

Cited by 17 publications

(14 citation statements)

References 7 publications

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“…The immune response was also higher in adult mice than in juvenile ones in most results, which mean that it could be age dependent. This is in agreement with [17], [18] who stated that CAP adjuvant induced a lower level of IgE when compared to alum adjuvant and with [19], [20] who observed a decreased level of local irritation in experimental animals.…”

Section: Discussionsupporting

confidence: 92%

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

Issa¹,

Salim²,

Zidan³

et al. 2014

IJCEA

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Abstract-The present study aim at studying the histological effects of both aluminum phosphate (Alum) and calcium phosphate (CAP) nanoparticles adjuvant in parallel with their potentials as adjuvant and the related immune response to tetanus toxoid vaccine adsorbed on both of them. Ninety Swiss albino mice were used in the experiment (50% adults and 50% juveniles). Mice were immunized intramuscularly with 0.125 ml adjuvanted tetanus toxoid vaccine. For alum adjuvant study, 27 adult mice and 27 juvenile ones were injected with alum adjuvanted vaccine and sacrificed weekly as triplects for 9 weeks. For calcium phosphate adjuvant study, 15 adult mice and 15 juvenile ones were injected with calcium phosphate adjuvanted vaccine and sacrificed weekly as triplects for 5 weeks. The effect of alum and calcium phosphate nanoparticles adjuvants in enhancing the immune response of tetanus toxoid vaccine were monitored through measurement of antibody titer in sera of mice. The pathological effect of both adjuvants were monitored through histological study of liver, brain, kidney and injected muscle of sacrificed animals. Recorded data revealed that both adjuvanted vaccine caused histopathological changes in tissues of liver, kidney, brain and injected muscle. On the other hand alum adjuvanted tetanus toxoid vaccine was more potent and showed higher antibody level than CAP adjuvanted vaccines.

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Section: Discussionsupporting

confidence: 92%

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

Issa¹,

Salim²,

Zidan³

et al. 2014

IJCEA

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“…We have analyzed CAP at 4°C, room temperature, 37°C, and 50°C for a 6-month period and observed no significant changes in pH, size, or surface morphology (data not shown). Earlier studies have reported that CAP adjuvant, in comparison with alum adjuvant, induced a lower level of IgE, decreased the level of local irritation in experiments with animals, and caused fewer variations in human clinical trials (5,11,18,20). Our preclinical toxicity and animal studies confirmed that only minor inflammation occurred at the injection sites in guinea pigs during the first 2 weeks and that CAP did not elicit IgE responses.…”

Section: Discussionmentioning

confidence: 99%

“…Although they effectively enhance immune responses, there are several disadvantages associated with their use (3,5,14). The disadvantages of alum-based adjuvants include the severity of local tissue irritation, the longer duration of the inflammatory reaction at the injection site, strong Th2 responses, minimal induction of cell-mediated immunity, and a propensity to elicit undesirable immunoglobulin E (IgE) responses (11,12,17,27). Alum compounds have also been shown to increase the levels of potential undesirable homocytotropic antibodies in animal species (9, 21).…”

mentioning

confidence: 99%

Calcium Phosphate Nanoparticle Adjuvant

He¹,

Mitchell²,

Johnson³

et al. 2000

Clin Diagn Lab Immunol

198

139

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Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.Historically, adjuvants have been necessary to improve vaccine efficacy in order to afford protection against infections. A key reason for this is that both attenuated virus preparations and, particularly, recombinant proteins are often poorly antigenic. In the past decade, several adjuvants have been evaluated in clinical trials. Calcium phosphate (CAP), MF59, aluminum (alum) compounds, and virosomes have been approved for human use in several European countries (23). In the United States, alum compounds are the most extensively used adjuvants in licensed vaccines for humans. Although they effectively enhance immune responses, there are several disadvantages associated with their use (3,5,14). The disadvantages of alum-based adjuvants include the severity of local tissue irritation, the longer duration of the inflammatory reaction at the injection site, strong Th2 responses, minimal induction of cell-mediated immunity, and a propensity to elicit undesirable immunoglobulin E (IgE) responses (11,12,17,27). Alum compounds have also been shown to increase the levels of potential undesirable homocytotropic antibodies in animal species (9, 21). Furthermore, alum-based vaccines are frequently ineffective for the induction of antiviral immunity (4). For these reasons, new adjuvants are being developed to enhance the immunity against weak antigens. New-generation adjuvants are designed to induce minimal side effects, enhance the duration of the immune response, and concurrently stimulate humoral, cellular, and mucosal immune responses. Furthermore, an ideal adjuvant would be biodegradable, economical, and simple to manufacture. In addition, it would have the potential to selectively trigger a defined class of immune response such as the T-helper 1 (Th1) CD4 ϩ T-cell response and cell-mediated immunity and have equal applicability for any new-genera...

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“…Calcium phosphate has also been used for allergen desensitization (6, 16). Early studies indicated that calcium phosphate particles produce strong adjuvant effects, induced less immunoglobulin E (IgE) than aluminum adjuvants, and elicited only minimal local irritation in animal experiments and human clinical trials (6,8,11,17).Here, we describe a unique formulation of calcium phosphate nanoparticles (CAP) which is distinct from the formulations of calcium phosphate described by European scientists (16) and demonstrate its use as an effective mucosal adjuvant. Our results indicate that following viral challenge, mice immunized with CAP-based formulations of herpes simplex virus type 2 (HSV-2) glycoprotein exhibited significantly increased survival rates and less severe clinical infection than controls.…”

mentioning

confidence: 90%

mentioning

confidence: 99%

Calcium Phosphate Nanoparticles Induce Mucosal Immunity and Protection against Herpes Simplex Virus Type 2

He¹,

Mitchell²,

Morçöl³

et al. 2002

Clin Vaccine Immunol

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Previously we reported that calcium phosphate nanoparticles (CAP) represented a superior alternative to alum adjuvants in mice immunized with viral protein. Additionally, we showed that CAP was safe and elicited no detectable immunoglobulin E (IgE) response. In this study, we demonstrated that following mucosal delivery of herpes simplex virus type 2 (HSV-2) antigen with CAP, CAP adjuvant enhanced protective systemic and mucosal immunity versus live virus. Mice were immunized intravaginally and intranasally with HSV-2 protein plus CAP adjuvant (HSV-2؉CAP), CAP alone, phosphate-buffered saline, or HSV-2 alone. HSV-2؉CAP induced HSV-specific mucosal IgA and IgG and concurrently enhanced systemic IgG responses. Our results demonstrate the potency of CAP as a mucosal adjuvant. Furthermore, we show that systemic immunity could be induced via the mucosal route following inoculation with CAP-based vaccine. Moreover, neutralizing antibodies were found in the sera of mice immunized intranasally or intravaginally with HSV-2؉CAP. Also, the results of our in vivo experiments indicated that mice vaccinated with HSV-2؉CAP were protected against live HSV-2 infection. In conclusion, these preclinical data support the hypothesis that CAP may be an effective mucosal adjuvant that protects against viral infection.Since mucosal surfaces act as the primary point of entry for most pathogens and the first line of defense against them, vaccines inducing effective mucosal immunity may reduce rates of infection and decrease the morbidity and mortality of infectious diseases. Currently, no safe and effective mucosal vaccine adjuvants are approved for human use.Mucosal vaccine delivery is a promising strategy. Mucosal vaccines administered in one part of the body can elicit an antibody response in mucosal tissues remote from the site of initial antigen exposure. This effect occurs because of the common mucosal immune system (13). A major obstacle to developing a mucosal vaccine in humans is finding a safe and effective adjuvant. Experimental mucosal adjuvants include cholera toxin, heat-labile enterotoxin, mutant toxins (LTK63 and LTR72), CpG oligodeoxynucleotide, polymerized liposomes, microparticles, and interleukins or immune modulators. None of these adjuvants is approved for use in humans (3,12,18).Biodegradable calcium phosphate particles have been investigated as an alternative to aluminum adjuvants for parenteral vaccines. Clinical studies conducted in France described the use of a calcium phosphate adjuvant for secondary or booster immunizations against diphtheria and tetanus (8). Calcium phosphate has also been used for allergen desensitization (6, 16). Early studies indicated that calcium phosphate particles produce strong adjuvant effects, induced less immunoglobulin E (IgE) than aluminum adjuvants, and elicited only minimal local irritation in animal experiments and human clinical trials (6,8,11,17).Here, we describe a unique formulation of calcium phosphate nanoparticles (CAP) which is distinct from the formulations of calciu...

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Calcium-phosphate-adjuvanted allergens: Total and specific IgE levels before and after immunotherapy with house dust and Dermatophagoides pteronyssinus extracts

Cited by 17 publications

References 7 publications

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

Calcium Phosphate Nanoparticle Adjuvant

Calcium Phosphate Nanoparticles Induce Mucosal Immunity and Protection against Herpes Simplex Virus Type 2

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