Ovarian cancer is the fifth most leading cause of cancer related deaths in women in the US. Customized immunotherapeutic strategies may serve as an alternative method to control the recurrence or progression of ovarian cancer and to avoid severe adverse effects of chemotherapy. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared with the use of a spray dryer. These particles were designed for oral delivery using enteric polymers such as methacrylic copolymer, Eudragit(®) FS30D and hydroxyl propyl methyl cellulose acetate succinate. These particles were targeted for uptake via microfold cell (M-cell) in Peyer's patches of small intestine using M-cell targeting ligand, Aleuria aurantia lectin. The interleukins (ILs) such as IL-2 and IL-12 were added to the vaccine formulation to further enhance the immune response. The particles obtained were of 1.58±0.62 μm size with a charge of 12.48±2.32 mV. The vaccine efficacy was evaluated by administering the particles via oral route to C57BL/6 female mice. At the end of vaccination, mice were challenged with live tumor cells. Vaccinated mice showed significant (around six-fold) retardation of tumor volume in comparison to non-vaccinated animals for 3 weeks after the tumor challenge (p<0.001). The serum IgG antibody levels were found to be elevated in case of vaccinated animals in comparison to non-vaccinated group (p<0.05). Analysis of IgG1 titers (indicative of Th2 response) and IgG2a titers (indicative of Th1 response) showed a mixed Th1 and Th2 immune response in case vaccine alone and Th2 response in case of vaccine with interleukins group. Moreover, CD8+ T-cell, CD4+ T-cell and B-cell populations in different lymphatic organs were elevated in case of vaccinated mice. Thus, whole cell lysate vaccine microparticles formulated by spray drying could trigger humoral as well as cellular immune response when administered orally. Such vaccine could potentially be an effective treatment for patients with residual tumor or high tumor-relapse probability.
[Show abstract][Hide abstract] ABSTRACT: Sperm protein (Sp17) is an attractive target for ovarian cancer (OC) vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17) was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.
PLoS ONE 05/2010; 5(5):e10471. DOI:10.1371/journal.pone.0010471 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral vaccination has long been regarded as the best alternative to conventional parenteral vaccination considering practical, economical, and immunological aspects. The purpose of this study was to develop albumin-chitosan mixed matrix microsphere-filled coated capsule formulations of Typhoid Vi antigen and to determine whether it can induce antigen-specific mucosal and systemic immune responses on oral administration. Formulations with Typhoid Vi antigen were prepared and filled into hard gelatin capsules (size # 9) and enteric coated. Formulations were characterized and administered to Sprague-Dawley rats to evaluate the induction of immune response to the antigen. The results indicated that the particle size, zeta potential, swelling, and disintegration rates were optimal for the oral delivery of microencapsulated vaccines. In vivo studies displayed multifold increase of antigen-specific IgG and IgA levels 8 weeks after oral immunization. No statistically significant difference in the antigen-specific IgG and IgA levels were found between oral and parenteral injection groups 8 weeks after vaccination. On the basis of the results of the study, it can be concluded that the oral administration of Typhoid Vi antigen microspheres was successful in inducing antigen-specific systemic and mucosal immune response.
Journal of Drug Targeting 07/2009; 17(7):553-60. DOI:10.1080/10611860903067301 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mucosal immunization has been suggested to be the best option for preventing Mycobacterium tuberculosis infection. The purpose of this study was to develop albumin microspheres containing Mycobacterium tuberculosis antigens and to determine if oral administration of the microspheres can induce antigen-specific mucosal and systemic immune responses. Albumin microspheres containing Mycobacterium tuberculosis dead cells and cell lysate were prepared. The physico-chemical characteristics of the formulations were determined and the microspheres were administered to animal models to evaluate the induction of immune responses to the antigens. The results showed that the particle sizes, zeta potential and dissolution pattern of the microspheres were ideal for oral delivery of vaccines. In vivo studies showed high production of antigen-specific antibody production in serum, nasal, salivary and faecal samples. From the results of the study, it can be concluded that oral administration of Mycobacterium tuberculosis microspheres was successful in inducing antigen-specific systemic and mucosal immune responses.
Journal of Microencapsulation 07/2008; 26(2):166-79. DOI:10.1080/02652040802211717 · 1.59 Impact Factor
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