Very Small Size Proteoliposomes (VSSP) and Montanide combination enhance the humoral immuno response in a GnRH based vaccine directed to prostate cancer

Aguilar, Franklin Fuentes; Barranco, Jesús Junco; Fuentes, Eddy Bover; Aguilera, Lesvia Calzada; Sáez, Yovisleydis Lopez; Santana, María Dolores Castro; Vázquez, Eulogio Pimentel; Baker, Roberto Basulto; Acosta, Osvaldo Reyes; Pérez, Hilda Garay; Nieto, Gerardo Guillén

doi:10.1016/j.vaccine.2012.08.020

Cited by 18 publications

(23 citation statements)

References 13 publications

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“…GnRH-based vaccines represent a promising anti-hormonal alternative treatment for patients with prostate cancer, since they reduce serum testosterone levels, leading to the generation of a memory immune response in vaccinated individuals (6,(10)(11)(12). However, the poor immunogenicity of small and autologous peptides, such as GnRH and its mimetics, is a challenging obstacle that must be overcome by immunologists (10,11,24,25).…”

Section: Discussionmentioning

confidence: 99%

“…The development of the vaccine formulation GnRHm1-TT/Montanide ISA 51/VSSP is a promising candidate to generate a productive response against GnRH, which presents the advantage of combining a type 1 and a type 2 adjuvants (12,24). To investigate how this vaccine candidate affects a tumoral model, the present study performed an experiment in DD/S mice implanted with the hormone-sensitive SC 115 tumor cell line, which has been extensively used to study the conversion from androgen-dependent to androgen-independent neoplasia (7,21).…”

Section: Anti-gnrh Antibodies Generated By the Vaccine Candidate Gnrmentioning

confidence: 99%

“…In all 5 mice, 100% of anti-GnRH seroconversion was achieved following the administration of 2 immunizations (Table I). The anti-GnRH immune response was investigated using an in-house titration indirect ELISA method (6,12), which rendered titers between 1:1,000 and 1:4,000 (Table I). Similarly to the anti-GnRH immune response, the measurement of the testosterone levels by radioimmunoassay demonstrated a decrease in the testosterone concentration of the immunized animals, although the levels of testosterone in these animals were higher than those detected in the castrated mice (Table I).…”

Section: Anti-gnrh Antibodies Generated By the Vaccine Candidate Gnrmentioning

confidence: 99%

“…GnRH-based vaccines represent a promising anti-hormonal treatment alternative for the treatment of prostate cancer, since they reduce serum testosterone levels and avoid the flare response observed when using GnRH analogues (6,(10)(11)(12) procedure, the patient does not require the administration of any other medication for a prolonged period, which results in low costs (6,12). Therefore, these types of vaccines may be highly competitive in the market (10,11,13).…”

Section: Introductionmentioning

confidence: 99%

“…The combination of Montanide ISA 51, a type 1 adjuvant, and very small size proteoliposomes (VSSP), a type 2 adjuvant that is derived from the fermentation of Neisseria meningitides, has been recently used by the authors of the present study for the generation of anti-GnRH antibodies in healthy animals with excellent results (12).…”

Section: Introductionmentioning

confidence: 99%

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Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

et al. 2016

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Abstract. In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19-31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. IntroductionProstate cancer is the most commonly diagnosed malignancy in elderly men, and the second leading cause of cancer-associated mortality in the Western world (1,2).Standard treatments for prostate cancer include surgery, radiation therapy and androgen deprivation therapy (ADT), which are usually successful in controlling organ-confined disease. However, in 30% of patients the disease recurs and becomes androgen deprivation-resistant (3,4).Since the 1990's, gonadotropin-releasing hormone (GnRH) analogues have been the most successful drugs for achieving ADT (5). Androgen is required for the function and maintenance of prostate cancer cells, and androgen deprivation results in an inhibition of growth and decrease in volume of prostate cancer tumors (6-8). However, at advanced stages of the disease, almost all tumors develop into castration-resistant prostate cancer (CRPC), the management of which is a great challenge (6,8,9). Consequently, there is a clear requirement for improved treatments to prevent the development of CRPC, and for novel therapies to treat patients with prostate cancer.GnRH-based vaccines represent a promising anti-hormonal treatment alternative for the treatment of prostate cancer, since they reduce serum testosterone levels and avoid the flare response observed when using GnRH analogues (6,10-12). In addition, follo...

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Section: Discussionmentioning

confidence: 99%

Section: Anti-gnrh Antibodies Generated By the Vaccine Candidate Gnrmentioning

confidence: 99%

Section: Anti-gnrh Antibodies Generated By the Vaccine Candidate Gnrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

et al. 2016

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Single‐Shot Mesoporous Silica Rods Scaffold for Induction of Humoral Responses Against Small Antigens

Dellacherie

et al. 2020

Adv Funct Materials

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Vaccines have shown significant promise in eliciting protective and therapeutic responses. However, most effective vaccines require several booster shots, and it is challenging to generate responses against synthetic molecules and peptides often used to increase target specificity and improve vaccine stability. As continuous antigen uptake and processing by antigen‐presenting cells and persistent toll‐like receptor priming can amplify humoral immunity, it is explored whether a single injection of a mesoporous silica micro‐rod (MSR) vaccine containing synthetic molecules and peptides can generate potent and durable humoral immunity. A single injection of the vaccine targeting a gonadotropin‐releasing hormone (GnRH) decapeptide elicits high anti‐GnRH titer for over 12 months and generated higher titers than bolus or alum formulations. Targeting a Her2/neu peptide within the Trastuzumab binding domain causes immunoreactivity to Her2 on tumor cells and, MSR vaccines against nicotine generated long‐term anti‐nicotine antibodies. A single MSR injection induced germinal center (GC) activity for more than 3 weeks, generated memory B cells, and 7 days of immunostimulation by the vaccine is required to generate effective antibody responses. The MSR vaccine represents a promising technology to bypass the need for multiple immunizations and enhance long‐term antibody production in the context of reproductive biology, cancer, and chronic addiction.

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Scaffold Vaccines for Generating Robust and Tunable Antibody Responses

Najibi

Dellacherie

Shih

et al. 2022

Adv Funct Materials

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Traditional bolus vaccines often fail to sustain robust adaptive immune responses, typically requiring multiple booster shots for optimal efficacy. Additionally, these provide few opportunities to control the resulting subclasses of antibodies produced, which can mediate effector functions relevant to distinct disease settings. Here, it is found that three scaffold-based vaccines, fabricated from poly(lactide-co-glycolide) (PLG), mesoporous silica rods, and alginate cryogels, induce robust, long-term antibody responses to a model peptide antigen gonadotropin-releasing hormone with single-shot immunization. Compared to a bolus vaccine, PLG vaccines prolong germinal center formation and T follicular helper cell responses. Altering the presentation and release of the adjuvant (cytosine-guanosine oligodeoxynucleotide, CpG) tunes the resulting IgG subclasses. Further, PLG vaccines elicit strong humoral responses against disease-associated antigens HER2 peptide and pathogenic E. coli, protecting mice against E. coli challenge more effectively than a bolus vaccine. Scaffold-based vaccines may thus enable potent, durable and versatile humoral immune responses against disease.

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Very Small Size Proteoliposomes (VSSP) and Montanide combination enhance the humoral immuno response in a GnRH based vaccine directed to prostate cancer

Cited by 18 publications

References 13 publications

Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

Single‐Shot Mesoporous Silica Rods Scaffold for Induction of Humoral Responses Against Small Antigens

Scaffold Vaccines for Generating Robust and Tunable Antibody Responses

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