A new method to use a pathogen to generate a vaccine for another pathogen

Description

[0001] A New method to use a pathogen to generate a vaccine for another pathogen

[0002] Technical Field

[0003] (1) A new method to use one pathogen to produce a vaccine for another pathogen

[0004] (2) As well as a new method for treating diseases by using the effect of a specific antigen and delivering it by viral or non- viral harmless means to the body to use this desired effect to treat other diseases caused by other pathogens and avoid stimulating any immune-related side effects or any other effect of the antigen.

[0005] Prior Art

[0006] (3) Current treatments for chronic secondary immunodeficiency diseases target the pathogen itself,

[0007] (4) And consider that the disease is due to a direct harmful effect of the pathogen.

[0008] (5) The common belief that the complications are due to the pathogen itself.

[0009] Summary of the Invention

[0010] (6) We have developed a new method to treat immunodeficiency diseases and meet all functional cure requirements without stimulating any immune-related side effects by using a non-replicating viral vector that does not infect humans.

[0011] (7) We have developed the method by which a vaccine is obtained using a pathogenic agent and used to provide a complete functional cure (1) for a disease caused by a different pathogen through the concept of strengthening the immune system’s defenses sufficiently and only enough to provide this (5) complete functional cure.

[0012] Technical Problem in the Prior Art

[0013] (8) Many chronic diseases are essentially due to the inability of current treatments to meet all the requirements to achieve a functional cure (they meet only some of them), or because current treatments will stimulate and cause serious negative immune-related events (2).

[0014] (9) Chronic complications are primarily due to the interaction between the pathogen and the body's immunity, not the pathogen itself, and result from this interaction and not from a direct harmful effect of the pathogen.

[0015] (10) We must think of the new concept of carefully verifying the effect of the pathogen on the body: is it a direct harmful effect, or does it result from the interaction between the body and the pathogen?

[0016] (11) In many diseases and complications, chronic complications are due to a misunderstanding of the disease pathophysiology, leading to targeting the symptoms instead of the root causes (3), in addition to the common belief that the complications are due to the pathogen itself and not the interaction with the body’ s immunity.

[0017] (12)This interaction will change the body’s immunity (4), and therefore all treatments that fight this pathogen will be disrupted because the body's immunity changes and will not perform its optimal function or may not even be able to recognize the pathogen.

[0018] (13) 1. Chronic Hepatitis B

[0019] (14) Treatments: Antivirals such as Tenofovir aim to control hepatitis B virus (8). More recent approaches, such as therapeutic vaccines and (9) RNA interference therapies, are under development.

[0020] (15) Innovations: Patents focus on new drugs such as Bulevirtide (10) and advanced delivery systems.

[0021] (16) 2. AIDS (HIV)

[0022] (17) Treatments: Combination therapies such as Biktarvy and long-acting drugs such as Sentence are the standard. Research explores mRNA vaccines for prevention and treatment (11).

[0023] (18) Innovations: Patented therapies include long-acting injectable inhibitors (12) and envelope inhibitors targeting resistant strains. (19) 3. Herpes (HSV)

[0024] (20) Treatments: Acyclovir and Vai acyclovir remain the primary treatments. Emerging therapies focus on gene-editing technologies (13) such as CRISPR to target latent viruses.

[0025] (21) Innovations: Patents (14) are submitted for gene-editing and innovative delivery mechanisms.

[0026] (22) 4. Cancer-related immunodeficiency

[0027] (23) Treatments: Immunotherapies such as checkpoint inhibitors (e.g., Pembrolizumab) restore immune function against tumors (15).

[0028] (24) Innovations: Patents (16) emphasize combination therapies to enhance efficacy and reduce complications.

[0029] (25) These are the current treatments for secondary immunodeficiency disorders which face many mitigations (18), including:

[0030] (26) 1. Underlying causes: Difficulty addressing root causes such as infection, cancer, or malnutrition.

[0031] (27) 2. Infections: Recurrent infections (19) complicate treatment and recovery.

[0032] (28) 3. Immune restoration: (20) Limited ability to fully restore immune function.

[0033] (29) 4. Treatment side effects (21): Immunosuppressive drugs may worsen the condition.

[0034] (30) Current treatments can achieve only one criterion but cannot address the other challenges.

[0035] (31) Treatments will improve the condition and may alleviate or treat some or all symptoms. The only truth is that they do not provide a cure. (22) Furthermore, most of them will lead to immune-related adverse events (23).

[0036] Technical Solution

[0037] (32) Current treatments can achieve only one criterion but cannot address the other challenges associated with or caused by general immunosuppression, with an accurate understanding of the disease pathophysiology of secondary immunodeficiency involving immunosuppression or impaired function due to underlying disease, infection, malnutrition, aging, or drugs.

[0038] (33) This leads to impaired immune cell production, reduced cytokine signaling, and immune cell depletion, making patients more vulnerable to infections, cancer, and inflammatory complications.

[0039] (34) These complications are associated with general immune weakness, creating a vicious cycle of infection susceptibility, chronic inflammation, and immune dysregulation — all of which enhance the chronic nature of immunodeficiency diseases and limit the possibility of curing them (24).

[0040] (35) Current treatments aim to reduce infection risk, manage autoimmune complications, and improve overall quality of life. However, many challenges (25) still face effective treatment of these conditions.

[0041] (36) Treatments will improve the condition and may alleviate or treat some or all symptoms. The only truth is that they do not provide a cure. Furthermore, most will lead to immune-related adverse events.

[0042] (37) With our method, we can deliver an immune-enhancing antigen into the bodies of these immunodeficient patients to use this effect to treat secondary immunodeficiency disorders (26).

[0043] (38) Our new method is based on using the effect of a specific antigen and delivering it by harmless viral (6) or non- viral means to the body to use this desired effect to treat other diseases caused by other pathogens and avoid stimulating any immune-related side effects or any other effect of the antigen.

[0044] (39) With our new method, we can identify a specific effect of any drug that meets all functional cure criteria for another disease, then deliver it into the body using genetically modified harmless means — e.g., non-replicating viral or non- viral vectors — as a vehicle to deliver this antigen to the body to use its effect, and it can also be stated that the antigen will simultaneously avoid any immune-related side effects. (40) The antigen used is selected so that it produces the desired effect to achieve or meet all functional cure criteria or requirements necessary to combat and eliminate the targeted antigens.

[0045] (41) To apply our new method to secondary immunodeficiency diseases (7), the drug causes the desired effect and induces changes to enhance immunity.

[0046] (42) It must stimulate the following effects: Type I and acquired helper T cells, as well as stimulating the response of releasing signaling molecules called cytokines and chemokines, which lead to local inflammation and attract immune cells to the site.

[0047] (43) Dendritic cells and macrophages (antigen-presenting cells) capture the antigen (27) and present it to T cells in the lymph nodes, which is crucial to initiating the adaptive immune response (28).

[0048] (44) Activation of B cells (29) and production of antibodies (30).

[0049] (45) B cells that recognize the antigen are activated and begin producing antibodies, especially IgM antibodies, which are the first type of antibody response produced by the body.

[0050] (46) Activation of T cells (31): Antigen presentation leads to activation of T cells :

[0051] (47) Helper T cells (CD4+) help B cells produce more antibodies (32)(33) and B- memory cells .

[0052] (48) Cytotoxic T cells (CD8+) acquire the ability to identify and destroy infected cells.

[0053] (49) After this initial exposure, B and T memory cells form. These memory cells remember the antigen (34), allowing a faster and stronger response upon subsequent exposure (e.g., second dose or actual infection).

[0054] (50) This booster dose leads to a much stronger response due to the presence of B and T memory cells created by the first dose.

[0055] (51) 2. Enhancing Antibody Production:

[0056] (52) Increasing IgG antibodies:

[0057] (53) The second dose (36) stimulates a strong production of high-affinity IgG antibodies, which are more specific and effective than the primary IgM antibodies produced after the first dose. (54) B cells undergo a process called affinity maturation (35), where they become more precise in targeting the antigen. This results in antibodies that bind more tightly to the virus, improving vaccine effectiveness.

[0058] (55) Enhancing T-cell Response:

[0059] (56) Helper T cells (CD4+):

[0060] (57) The second dose further stimulates these cells, which continue to support antibody production by B cells.

[0061] (58) Cytotoxic T cells (CD8+):

[0062] (59) The booster dose enhances the cytotoxic T-cell response, enabling these cells to effectively identify (37) and kill infected cells.

[0063] (60) More memory T cells are produced, contributing to long-term immunity.

[0064] (61) Memory T cells respond quickly if the virus returns to the body, reducing the severity of possible infection.

[0065] (62) More memory T cells (38) are produced, contributing to long-term immunity. Memory T cells are important because they can respond quickly if the virus encounters the booster dose of immune memory created by the first dose.

[0066] (63) This memory includes both B-memory cells (which rapidly produce antibodies upon re-exposure) and T-memory cells (which help recognize and destroy infected cells).

[0067] (64) With our method, a drug with this effect can achieve all necessary criteria to achieve a functional cure for secondary immunodeficiency disorders without stimulating any serious immune-related side effects, and this is done using the effect of another antigen from another pathogen.

[0068] Advantages of the Invention

[0069] (65) With the new mechanism of action:

[0070] Therapeutic Benefits:

[0071] (66) The expected benefits from producing this drug according to the new mechanism of action include:

[0072] (67) 1 } providing a cure for many diseases permanently without the need for lifelong treatment. (68) 2} Treating different diseases as well as preventing them with the same drug.

[0073] (69) 3} Raising the general level of health care for citizens by eliminating many chronic diseases.

[0074] Economic Benefits:

[0075] (70) 4} providing job opportunities for many young people to work in pharmaceutical factories to produce this treatment.

[0076] (71) 5} saving foreign currency previously used to import drugs necessary for treating the diseases that this drug will treat.

[0077] (72) 6} Increasing the foreign currency reserve by exporting this drug, for which we exclusively own production rights for ten years.

[0078] (73) 7} providing the drug at affordable prices through the new method of action, which will save many manufacturing expenses.

[0079] Detailed Description of the Invention

[0080] (74) Our new method relies on using the effect of a specific antigen and delivering it by harmless viral or non- viral means to the body to use this desired effect to treat other diseases caused by other pathogens and avoid stimulating any immune- related side effects or any other effect of the antigen.

[0081] (75) With our new method, we can identify a specific effect for any drug that meets all criteria of functional cure for another disease, then deliver it to the body using harmless genetically modified means — for example, non-replicating viral or non- viral vectors — as a vehicle to deliver this antigen to the body to use its effect, and it can be stated that the antigen will simultaneously avoid immune-related side effects.

[0082] (76) The antigen used is selected such that it produces the desired effect to achieve or meet all criteria or requirements of functional cure necessary to combat and eliminate the targeted antigens. Examples

[0083] (77) The following example is an example of using the drug's effect without causing harm, using a non-homologous animal viral vector to treat another disease caused by different pathogens.

[0084] (78) The Vaxzevria vaccine (AstraZeneca COVID-19 vaccine) is prepared from the spike protein antigen of SARS-CoV-2, which uses a non-homologous chimpanzee adenoviral vector (39) as a means to deliver the antigen.

[0085] (79) Using our new method, our company will use its immune effect on innate and adaptive immunity (arising from giving two doses with separate effects on immunity). Our company will use this immune effect to treat secondary immunodeficiency diseases.

[0086] (80) This is an example of using the effect of an antigen from one disease to treat another disease using a non-homologous animal viral vector as a means of delivering the antigen.

[0087] (81) This technique, which applies our company's new method, is applied in Vaxzevria, making it superior to other treatments for immunodeficiency diseases because it is the only drug that meets five essential needs for successful functional cure:

[0088] (82) 1 } It will stop viral replication and eliminate viral antigens through its effect on cccDNA.

[0089] (83) 2} In addition to no further detection (levels of viral DNA).

[0090] (84) 3 } It will overcome immune tolerance and immune evasion.

[0091] (85) 4} it will eliminate viral reservoirs by suppressing cccDNA.

[0092] (86) 5} the effect of Vaxzevria using this technique has been reported without any immune-related side effects.

[0093] (87) Our company is the first to reuse the Vaxzevria vaccine to treat secondary immunodeficiency diseases using this concept and using the immune effect resulting from both injections together, which will meet all functional cure requirements without stimulating any immune-related adverse events. (88) No immune-related side effects will develop.

[0094] (89) The use of a non-replicating adenoviral vector like that in the Vaxzevria vaccine (AstraZeneca COVID-19 vaccine) can indeed help reduce the risks of immune-related side effects compared to a replicating virus. Here is the explanation of this effect:

[0095] (90) 1. the non-replicating nature reduces uncontrolled immune activation.

[0096] (91) Non-replicating adenoviral vectors are designed to be replication-deficient, meaning they cannot replicate in the body. This limits the viral load delivered by the vaccine, reducing excessive immune activation.

[0097] (92) Because the vector does not replicate, it avoids continuous stimulation of the immune system (40), reducing the risks of inflammatory responses and immune- related adverse events such as cytokine storms or prolonged inflammation.

[0098] (93) 2. Reduced risk of reactivation or triggering latent infections:

[0099] (94) Some live or replicating viral vectors can reactivate latent infections in immunocompromised individuals. The non-replicating adenovirus does not replicate, making it safer for people with weakened immune systems.

[0100] (95) 3. Reduced risk of immunity due to pre-existing immunity.

[0101] (96) Because non-replicating adenoviruses do not produce infectious viral particles, they are less likely to be strongly recognized by memory immunity compared to replicating viruses. This is especially beneficial for individuals who may have pre-existing immunity to adenoviruses.

[0102] (97) 4. Improved control of dosage and immune activation:

[0103] (98) Since the viral vector does not replicate, its presence in the body is fully controlled by the administered dose.

[0104] (99) SARS-CoV-2 infection is a sepsis-like condition that begins with excessive immune activation and then progresses to a (41) late stage of immunosuppression.

[0105] (100) in our company’s new method, using the non-replicating chimpanzee adenovirus vector will limit the effect on the hyper-immune stage without developing sepsis and without progressing to the immunosuppression stage. (101) this excessive immune effect is the only effect that stimulates innate and adaptive immunity without stimulating any immune-related adverse events. (This is our company's concept.)

[0106] (102) while AstraZeneca used a chimpanzee adenoviral vector (42) for two main reasons:

[0107] (103) AstraZeneca used a chimpanzee adenoviral vector to produce its COVID-19 vaccine.

[0108] (104) because it is a harmless virus that does not infect humans. This choice reduced the risk of pre-existing immunity in humans, which could reduce vaccine effectiveness.

[0109] (105) additionally, adenoviral vectors are well- studied for safely delivering genetic material and stimulating a strong immune response.

[0110] (106) AstraZeneca did not use or apply the method to avoid immune-related side effects (43) or to treat any disease.

[0111] (107) AstraZeneca used Vaxzevria to prevent COVID-19 infection, not as a treatment or cure for any disease.

[0112] (108) in our company’s new method, we will use the immune effect of the spike protein delivered by a harmless non-replicating chimpanzee adenoviral vector to treat secondary immunodeficiency diseases.

[0113] (109) alongside our new method, the non-replicating chimpanzee adenoviral vector will be used to avoid stimulating any immune-related side effects.

[0114] (110) to obtain the desired immune effect of the antigen (spike protein) and use it to treat immunodeficiency diseases, we must consider the timing of the two injections.

[0115] (111) the timing of the two injections must be carefully considered as follows to obtain the optimal immune effect from the two doses:

[0116] (112) After the first dose of the Vaxzevria vaccine, the timeline for achieving optimal cytokine production and cytotoxic capability (key functions of T cells and innate immunity) unfolds over days to weeks, depending on the immune components involved. Timeline of cytokine production and cytotoxic capability:

[0117] (113) 1. Cytokine production

[0118] (114) early phase (hours to days):

[0119] (115) within hours to 1-3 days, the adenoviral vector (44) in the Vaxzevria vaccine activates innate immune sensors (such as Toll-like receptors), leading to rapid release of pro-inflammatory cytokines such as:

[0120] (116) Interferon-gamma (IFN-y): stimulates antiviral defenses.

[0121] (117) Tumor necrosis factor-alpha (TNF-a): enhances inflammation.

[0122] (118) Interleukins (such as IL-6 and IL-12): help activate adaptive immunity.

[0123] (119) Peak cytokine production:

[0124] (120) Cytokine production peaks within the first 3-5 days as part of the innate response (45), helping recruit and activate T cells and B cells.

[0125] (121) Continued cytokine release:

[0126] (122) Over the next 7-14 days, cytokine production shifts to adaptive immunity, dominated by T-cell-derived cytokines such as:

[0127] (123) IL-2: enhances T-cell proliferation.

[0128] (124) IFN-y: enhances cytotoxic T-cell activity (46) and activates macrophages.

[0129] (125) 2. Cytotoxic T-cell capability (CD8+ T cells)

[0130] (126) Initial activation (7-10 days):

[0131] (127) CD8+ cytotoxic T cells are activated and begin proliferating within 7-10 days after the first dose.

[0132] (128) these cells acquire the ability (47) to kill infected cells by releasing:

[0133] (129) Perforin: creates pores in membranes of infected cells.

[0134] (130) Granzyme: induces apoptosis in target cells.

[0135] (131) Peak cytotoxic activity (2-3 weeks):

[0136] Peak cytotoxic capability is observed about 2-3 weeks after vaccination (48), as

[0137] (132) CD8+ T cells expand and become fully functional. (133) Production of interferon- gamma by CD8+ T cells also peaks, enhancing antiviral activity.

[0138] (134) Memory phase (4+ weeks):

[0139] By 4-8 weeks, some CD8+ T cells transition to memory T cells, retaining cytotoxic potential for long-term protection.

[0140] (135) 3. Booster dose effect

[0141] (136) the second dose amplifies both cytokine production and cytotoxic T-cell responses. (49) Administering the second dose after 8-12 weeks ensures that memory T cells have fully developed, leading to:

[0142] (137) Increased cytokine production upon reactivation.

[0143] (138) Stronger and faster cytotoxic responses.

[0144] (139) Timeline Summary:

[0145] (140) 1. Cytokine production:

[0146] (141) Peaks within 3-5 days after the first dose for innate responses.

[0147] (142) Adaptive cytokines (e.g., IFN-y) peak around 1-2 weeks.

[0148] (143) 2. Cytotoxic T-cell activity:

[0149] (144) Begins around 7-10 days.

[0150] (145) Peaks within 2-3 weeks for effector T cells.

[0151] (146) Optimal long-term cytotoxic capability appears with memory T-cell maturation within 4-8 weeks.

[0152] (147) thus, while innate cytokine immune response is rapid, the adaptive immune system requires more time to acquire optimal and durable cytotoxic and cytokine- mediated effects.

[0153] (148) this indicates the following protocol to achieve the desired immune effect:

[0154] (149) A) the vaccine is injected into patients with any immunodeficiency diseases.

[0155] (150) B) Wait the minimum time needed to produce the optimal effect on innate immunity and prepare and stimulate the cytotoxic cells and necessary cells to produce optimal acquired immune stimulation. (151) C) Inject the patient with a second dose of the vaccine after 8-12 weeks from the first dose.

[0156] (152) Then clinical results of immunodeficiency diseases can be evaluated after 3- 4 weeks to assess the criteria for success in achieving functional cure.

[0157] Fields of Application of the Invention

[0158] (153) The new method that relies on using the effect of a specific antigen and delivering it by harmless viral or non- viral means to the body to use this desired effect to treat other diseases caused by other pathogens and avoid stimulating any immune-related side effects or any other effect of the antigen.

[0159] (154) this new method can be used to treat many chronic diseases so that they are treated and completely cured, and the patient does not need to take medication daily for life.

[0160] (155) But with the new method, the patient will need to take the treatment once or twice only to be completely cured permanently.

[0161] (156) Likewise for chronic complications, as they will be completely eliminated and removed through the new method that will use the appropriate and effective effect against these chronic complications to eliminate them.

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[0212] {49} Cross-reactive immunity to SARSE Cov-2 and related corona viruses https: / / ora.ox.ac.uk / objects / uuid:f240965c-c584-4326-ae9e-

[0213] 2ad3900a2902 / files / dn583xv61 f

Claims

Claims1. A method to deliver the antigen of any pathogen to the body by a harmless viral or non-viral mean to use the clinical effect of this antigen in the cure of a disease different than the disease the antigen extracted from its causing pathogen.

2. The method in claim 1 whereby the choice of the used antigen is such that it will produce the effect needed to achieve all criteria or requirements for the functional cure needed to combat and eradicate target antigens.

3. A method of developing a cure for immunodeficiency disorders: - a. We use a virus that does not infect humans as a viral vector; b. We make this virus non replicating; c. The gene for the SARS-COV-2 spike protein is inserted into the nonreplicating viral vector thus producing a modified viral vector; d. The modified viral vector is grown in an especially cultured human cell line known as HEK 293 (Human Embryonic Kidney cells) used to replicate the modified adenovirus; e. This replicated modified adenovirus is extracted from the cell culture; f. A purified extracted modified viral vector is generated by performing multiple purification steps of the modified viral vector to ensure that only the viral vector containing the spike protein gene remains; g. The purified extracted modified viral vectors are formulated with stabilizers, preservatives generating a stabilized preserved purified viral vector; h. The stabilized preserved purified extracted modified viral vector is adjusted to the desired concentration thus generating the vaccine; and i. The vaccine is packaged under sterile conditions.

4. The method in claim 3 whereby the virus used is the adenovirus of an animal.

5. The method of claim 4 whereby that animal is a chimpanzee.

6. The new method we developed will be used to achieve the cure of many chronic diseases or untreated chronic complications by using the desired effect of any drug, vaccine or any treatment to cure any disease or complication the original medicine not indicated or manufactured to cure it and in the same time using any harmless ways of delivering the antigen that will achieve the desired effect into viral vectors or non-viral harmful methods to deliver theantigen into the body then cure the disease we target without stimulating any immune-related adverse events and limiting the effect to the desired effect not the original effect of the drug the antigen used primarily with it.

7. 4} the viral vector used for the claim 2 is non-replicating adenovirus of chimpanzee.

8. The animal used for this claim 2 or claim 3 could be by harmless animal viral vectors include: -Adenovirus Vectors (Non-replicating), or Adeno- Associated Virus (AAV), or Lentivirus Vectors, or Modified Vaccinia Ankara (MVA), or Vesicular Stomatitis Virus (VSV) Vectors OR Non-viral and harmless methods include: Protein Subunit Vaccines, or DNA Vaccines, or mRNA Vaccines, or Nanoparticle-Based Delivery, or Microneedle Patches, or Inactivated Pathogen Vaccines, or Hydrogel Delivery Systems, or Exosome- Based Delivery.

9. Administrating the vaccine in the claim 4 according to a new protocol: - a) The vaccine is injected in the patients suffering from any immunodeficiency diseases. b) Waiting for the minimum time needed for establishing the optimum effect on the innate immunity and prepare and stimulate cytotoxic cells and the cells needed to establish optimum acquired immunity stimulation. c) Injecting the patient with a second dose of the vaccine.

10. The protocol in claim 9 further adding the step where the pathogen causing the immunodeficiency disease is injected into the patient after (3-4) weeks from the second dose of the vaccine.

11. The method in claim 9 where the waiting period between the two doses of the vaccine is 8- 12 weeks.

12. The method of claim 11 further adding the step where the pathogen causing the immunodeficiency disease is injected into the patient after (3-4) weeks from the second dose of the vaccine.

13. the pathogen causing the immunodeficiency disease will be injected one week before the second shot of the vaccine in claim 2 Or the pathogen causing the immunodeficiency disease will be injected (3-4) weeks after the second shot of the vaccine.

14. The method in claim 1 whereby the choice of the used antigen is such that it will produce the effect needed to achieve all criteria or requirements for the functional cure needed to combat and eradicate target antigens and their pathological effects.