Application of Forskolin or pharmaceutically acceptable salt thereof in preparation of vaccine immunopotentiator
By using Forskolin to promote high expression of CXCR4 in plasma cells, the shortcomings of existing vaccine adjuvants in regulating plasma cell lifespan and homing ability were overcome, resulting in a more durable and stable immune protection effect and avoiding adverse reactions.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-30
- Publication Date
- 2026-03-10
AI Technical Summary
Existing vaccine adjuvants mainly focus on enhancing the plasma cell production process, but lack direct regulation of plasma cell lifespan, homing ability, and residence capacity, resulting in poor immune memory persistence and potentially causing adverse reactions.
Using Forskolin or its pharmaceutically acceptable salts as adenosine cyclase activators directly promotes high expression of CXCR4 in plasma cells, enhancing their homing ability, residence capacity, and lifespan, thereby improving the long-term immune response of antibodies.
It significantly enhances the homing and residence capacity of plasma cells, prolongs their survival time in the bone marrow, improves the persistence of immune memory, and avoids the safety risks of traditional adjuvants.
Smart Images
Figure CN121622651A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of immunomodulatory technology, and more particularly to the use of Forskolin or its pharmaceutically acceptable salts in the preparation of vaccine immunostimulants. Background Technology
[0002] With the widespread use of vaccines for various infectious diseases and the continuous emergence of new pathogens, improving vaccine immunogenicity, prolonging protection time, and optimizing the quality of the immune response while ensuring safety has become one of the core issues in vaccine development. To this end, researchers have gradually introduced various vaccine immunomodulators, in addition to traditional vaccine antigen components, that can regulate the intensity and type of the body's immune response. Current vaccine immunomodulators mainly include adjuvants and immune enhancers. These substances enhance the immune response to the vaccine and improve its efficacy by activating the host's immune system.
[0003] The limitations of existing immunomodulators are also quite apparent. Traditional vaccine immunomodulators may have safety issues, causing local or systemic adverse reactions such as inflammation and allergic reactions. Furthermore, most vaccine immunomodulators primarily focus on regulating the production of plasma cells (antibody-secreting cells, key effector cells in vaccine immunization), for example, by enhancing germinal center responses and promoting B cell differentiation. While these strategies effectively enhance the immune response, they lack direct intervention in prolonging plasma cell lifespan, enhancing homing ability, and improving residence capacity. This means that traditional vaccine adjuvant technologies often struggle to sustain high levels of immune memory. Summary of the Invention
[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide the use of Forskolin or its pharmaceutically acceptable salts in the preparation of vaccine immune enhancers.
[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides the use of Forskolin or a pharmaceutically acceptable salt thereof in the preparation of vaccine immune enhancers.
[0006] Existing adjuvants primarily focus on enhancing plasma cell production, lacking direct means to regulate plasma cell lifespan, homing ability, and residence capacity, resulting in poor persistence of immune memory. Furthermore, traditional adjuvants may cause local or systemic adverse reactions, such as inflammation and allergic reactions. This invention addresses the shortcomings of existing vaccine immunomodulators by providing a novel method for enhancing vaccine efficacy using the natural plant extract Forskolin (as an adenylate cyclase activator). Forskolin significantly enhances plasma cell homing ability, residence capacity, and lifespan by promoting high expression of CXCR4 in plasma cells, thereby improving long-term antibody immune responses. Forskolin directly targets plasma cells, the effector cells of vaccine immunization, avoiding the safety risks of traditional techniques while providing more durable and stable immune protection.
[0007] Preferably, the immune enhancer improves long-term antibody levels and the persistence of immune memory by enhancing the homing ability, residence ability and / or lifespan of plasma cells after vaccination.
[0008] Preferably, the vaccine includes vaccines for humans or animals.
[0009] Preferably, the types of vaccines include inactivated vaccines, live attenuated vaccines, subunit vaccines, recombinant vaccines, nucleic acid vaccines, and vector vaccines.
[0010] In a second aspect, the present invention provides a vaccine immune-enhancing composition comprising Forskolin or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
[0011] Preferably, the vaccine immune-enhancing composition further includes other vaccine immunomodulators.
[0012] Preferably, the dosage form of the vaccine immune-enhancing composition includes an injectable or oral formulation.
[0013] Preferably, the vaccine immune enhancement composition is used to assist vaccine immunization to prolong the duration of immune protection and enhance the long-term immune effect of the vaccine.
[0014] Thirdly, the present invention provides a method for enhancing an individual’s immune response to a vaccine, comprising the step of administering an effective amount of Forskolin or a pharmaceutically acceptable salt thereof during or after vaccination of the subject.
[0015] Preferably, the method of administration includes injection or oral administration.
[0016] The beneficial effects of this invention are as follows: This invention provides a novel strategy based on existing vaccine immunomodulator technologies, focusing on directly regulating plasma cell function rather than simply enhancing plasma cell production. Forskolin, an adenylate cyclase activator, induces high expression of CXCR4 in plasma cells by promoting elevated cAMP levels. This significantly enhances plasma cell homing ability and promotes their residence and long-term survival in the bone marrow.
[0017] Unlike traditional vaccine adjuvants, which primarily modulate the pro-immune response through B cells and Tfh cells, Forskolin offers a unique advantage in maintaining immune memory by directly enhancing the physiological function of plasma cells and prolonging their lifespan in the bone marrow. This mechanism not only improves long-term immune protection but also avoids potential safety issues associated with traditional immunomodulators, such as local or systemic adverse reactions. Attached Figure Description
[0018] Figure 1 The results show the serum anti-NP IgG1 antibody concentration in the injection treatment group.
[0019] Figure 2 The results show the serum anti-NP IgG1 antibody concentration in the oral treatment group.
[0020] Figure 3 The figure shows the results of flow cytometry analysis of CXCR4 expression levels in plasma cells. Detailed Implementation
[0021] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.
[0022] Unless otherwise specified, the experimental methods used in this invention are conventional methods, and the materials and reagents used are commercially available products.
[0023] The NP-KLH was purchased from Biosearch Technologies; the Forskolin was purchased from Selleck, part number S2449.
[0024] Example 1: Effects of intraperitoneal injection of Forskolin and Vehicle on immune response in mice Experimental methods: 1. Inject mice (C57BL / 6, the same below) with the immune model antigen NP-KLH. NP-KLH is a commonly used model antigen in vaccine immunization research, which can simulate the T cell-dependent antibody response in the vaccine immunization process.
[0025] 2. Subsequently, for 30 consecutive days, patients received intraperitoneal injections of Vehicle (control group, 1.2% EDTA) or Forskolin (dose 2.5 mg / kg), both in PBS solution.
[0026] 3. At weeks 4, 8, 12, 16, 20, 24 and 28 post-vaccination, mouse serum was collected to measure changes in antibody levels (anti-NP IgG1).
[0027] Experimental results are as follows Figure 1 As shown, mice injected with Forskolin consistently had significantly higher levels of anti-NPIgG1 antibodies in their serum than those in the Vehicle group throughout the observation period. This indicates that Forskolin can effectively improve the persistence of the immune response and enhance the sustained production of antibodies.
[0028] Example 2: Effects of feeding mice with Forskolin-containing food on their immune response Experimental methods: 1. Mice were immunized with the immune pattern antigen NP-KLH to mimic the vaccine immunization process.
[0029] 2. Mice in the Forskolin group were treated by oral administration of food containing Forskolin (1.25 g / kg of Forskolin), while mice in the Vehicle group were given regular food without Forskolin, to simulate the way people use Forskolin supplements.
[0030] 3. At weeks 2, 4, 8, 12 and 16 post-vaccination, mouse serum was collected to measure changes in antibody levels (anti-NPIgG1).
[0031] Experimental results are as follows Figure 2 As shown, the serum anti-NPIgG1 antibody levels in mice injected with Forskolin were significantly higher than those in the Vehicle group throughout the observation period. This indicates that oral administration of Forskolin can effectively enhance the immune response and maintain long-term antibody levels.
[0032] In summary, this invention demonstrated, through two different administration methods (intraperitoneal injection and oral administration), that Forskolin significantly enhances the immune response.
[0033] Example 3: Mice were intraperitoneally injected for three consecutive days with either Vehicle (control group, 1.2% EDTA) or Forskolin (2.5 mg / kg), both in PBS solution. Bone marrow cells were collected immediately on the fourth day, and the expression level of CXCR4 on plasma cells was detected by flow cytometry. A significant increase in CXCR4 gMFI was observed. Figure 3 ).
[0034] This indicates that Forskolin treatment significantly enhances CXCR4 expression on the surface of plasma cells, which is beneficial for plasma cell homing, residence, and long-term survival.
[0035] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.
Claims
1. Use of forskolin or a pharmaceutically acceptable salt thereof in the preparation of a vaccine immune enhancer.
2. Use according to claim 1, wherein The immune enhancer enhances the homing ability, residence ability and / or life span of plasma cells after vaccination, thereby improving the long-term antibody level and immune memory persistence of vaccine immunity.
3. The use according to claim 1, wherein The vaccine includes vaccines for humans or animals.
4. A vaccine immune-enhancing composition, characterized by, The vaccine immune enhancer composition further comprises other vaccine immune modulators.
5. The vaccine immunopotentiating composition according to claim 4, wherein The dosage form of the vaccine immune enhancer composition includes injections, oral preparations.
6. The vaccine immunopotentiating composition according to claim 4, wherein The vaccine immune enhancer composition is used to assist vaccine immunity to prolong the time of immune protection and enhance the long-term immune effect of vaccines.
7. The vaccine immunoenhancing composition according to claim 4, wherein The vaccine immune enhancer composition is used to assist vaccine immunity to prolong the time of immune protection and enhance the long-term immune effect of vaccines.
8. A method of enhancing an individual's immune response to a vaccine, characterized in that, The vaccine immune enhancer composition is used to assist vaccine immunity to prolong the time of immune protection and enhance the long-term immune effect of vaccines.
9. The method of claim 8, wherein, The vaccine immune enhancer composition is used to assist vaccine immunity to prolong the time of immune protection and enhance the long-term immune effect of vaccines. The vaccine immune enhancer composition is used to assist vaccine immunity to prolong the time of immune protection and enhance the long-term immune effect of vaccines.