Calcium Phosphate Nanoparticle Adjuvant

Abstract

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...

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

“…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.…”

Construction and Immunological Evaluation of Immunostimulatory Nanocomposites with Vaccine Potential

“…In the inorganic nano-adjuvant, people have more research on calcium nanoparticles; the results found that calcium nanoparticles as immune adjuvant have a unique advantage [14]. The nanoparticle CA can be used as an anti-idiotypic antibody NP30 for schistosomiasis vaccines.…”

Development of Vaccine Adjuvants: A Historical Perspective

“…Replacement of aluminum salts with calcium phosphate has long been described [199]. Efforts with calcium adjuvants have continued [200], and work with calcium phosphate nanoparticles has had some preclinical success [201]. Use of stearyl tyrosine has been described for a variety of antigens now in use with aluminum adjuvants, including tetanus toxoid [200], diphtheria toxoid [202], and recombinant hepatitis B [203].…”