Exploration phase Preclinical Clinical Phase I Clinical Phase II Clinical Phase III Listed Nasal Spray Seasonal Flu Vaccine (TW) Nasal Spray Covid-19 Vaccine Covid-19 Immunotherapy (TW) Respiratory Allergy Immunotherapy - Rhinitis (TW) Respiratory Allergy Immunotherapy - Asthma (TW) 鼻噴劑型季節性流感疫苗(TW) 鼻噴型新冠肺炎疫苗 新冠肺炎免疫治療(TW) 呼吸道過敏免疫治療-過敏性鼻炎(TW) 呼吸道過敏免疫治療-氣喘(TW)

Advantages of Intranasal Vaccines Most infectious diseases begin at mucosal surfaces—especially in the respiratory tract. Unlike traditional intramuscular vaccines, intranasal vaccines create a first line of defense directly at the site of pathogen entry by inducing secretory IgA antibodies. These antibodies not only block infection and reduce transmission but also exhibit broader cross-reactivity against viral variants due to their structural properties. Beyond superior immunological advantages, intranasal vaccines are needle-free, less invasive, and more cost-effective. They minimize needle-related anxiety, reduce medical waste, and lower the risk of secondary infections. These benefits have positioned intranasal vaccines at the forefront of next-generation immunization strategies. The COVID-19 pandemic further highlighted their importance, driving global recognition and investment in mucosal vaccine development. Challenges in Intranasal Vaccine Development The principle of vaccination is straightforward: present the immune system with antigens that safely elicit protective responses without causing disease. Achieving this without injection into blood or muscle, however, remains highly challenging. Developing an intranasal vaccine that is both safe and strongly immunogenic requires solving complex issues in formulation, delivery, and durability of immune protection. Advagene's Breakthrough in Intranasal Vaccines Advagene Biopharma has built a proprietary mucosal adjuvant platform that addresses long-standing bottlenecks in intranasal vaccine development. This platform technology is versatile, enabling the design of vaccines across multiple pathogens while offering convenient administration, simple storage, and added mucosal protection. Our first vaccine—a seasonal intranasal influenza vaccine—has successfully completed Phase II clinical trials in elderly adults (ages 61–70). Results demonstrated an excellent safety profile and, importantly, showed that the vaccine induced robust mucosal IgA antibodies lasting up to six months, in addition to strong serum IgG responses. These findings, published in international journals, mark a global first and have attracted significant attention. Building on this success, Advagene rapidly mobilized during the COVID-19 crisis, applying our platform to the development of an intranasal COVID-19 vaccine in collaboration with partners. Preclinical studies confirmed that the vaccine elicited both IgA and IgG responses, providing systemic and mucosal protection. Critically, by reducing viral shedding, our candidate has the potential to address the limitations of injectable vaccines in curbing transmission, making it a promising tool for future pandemic preparedness. At Advagene, we are redefining the future of vaccination—transforming needle-free intranasal delivery into a powerful platform to protect global health.    Intranasal vaccines can induce IgA antibodies and tissue-resident memory lymphocytes in the respiratory mucosa, which injectable vaccines cannot achieve. Clinical trials have confirmed that Advagene's intranasal vaccine induces virus-neutralizing mucosal IgA antibodies that persist for over six months.

Allergic asthma is a chronic airway inflammatory disease that is characterized by eosinophil infiltration, bronchial epithelium damage, and airway hyperreactivity (AHR), which result from pathogenic Th2-type immune responses to environmental allergens, such as house dust mites (HDM; Dermatophagoides sp.)[Nat Med 18:716-725 (2012)]. Hypersensitivity to HDM is one of the most common allergic responses [Curr Opin Allergy Clin Immunol 9:128-135 (2009)] and >50% of children and adolescents with asthma are sensitized to HDM. Although allergen-specific CD4+ Th2 cells orchestrate the HDM allergic response through their induction of IgE directed against mite allergens, activation of innate immune responses, such as by dendritic cells (DCs) in the airway mucosa, also plays a critical role in HDM-induced allergic inflammation [Allergy Asthma Immunol Res 5:68-74 (2013)]. Allergic asthma is a chronic airway inflammatory disease that is characterized by eosinophil infiltration, bronchial epithelium damage, and airway hyperreactivity (AHR), which result from pathogenic Th2-type immune responses to environmental allergens, such as house dust mites (HDM; Dermatophagoides sp.)[Nat Med 18:716-725 (2012)]. Hypersensitivity to HDM is one of the most common allergic responses [Curr Opin Allergy Clin Immunol 9:128-135 (2009)] and >50% of children and adolescents with asthma are sensitized to HDM. Although allergen-specific CD4+ Th2 cells orchestrate the HDM allergic response through their induction of IgE directed against mite allergens, activation of innate immune responses, such as by dendritic cells (DCs) in the airway mucosa, also plays a critical role in HDM-induced allergic inflammation [Allergy Asthma Immunol Res 5:68-74 (2013)]. We have investigated the effects of LTh(αK) in an allergic asthma murine model and its involvement in the maturation and function of DCs. Our results showed that intra-nasal administration of LTh(αK) or LTh(αK) in combination with HDM allergen, decreased AHR, and attenuated the cardinal features of allergen-induced airway inflammation. In addition, LTh(αK)/HDM also induced allergen specific IgA. These LTh(αK) effects may have resulted from modifying DCs functions to reverse allergic immune responses, as shown by our in vivo and in vitro results. Thus, a detoxified mutant form of LT, LTh(αK), may have clinical applications for allergy and asthma as an immune-modulator. Treatment of allergy-Symptomatic treatment Currently the preferred treatment Attenuate symptoms with anti-histamines, steroid nasal sprays and anti-leukotrienes Most effective for patients with mild allergy symptoms No curative effect Treatment of allergy-Immunotherapy treats the underlying cause of the allergy ♦Immunotherapy with allergen ♦Anti-IgE antibody (Xolair) @media (max-width: 1024px) { #header_tx{ margin-right: 0px !important; margin-left: 0px !important; margin-bottom: 15px !important; padding: 30px !important; } } Allergic asthma is a chronic airway inflammatory disease that is characterized by eosinophil infiltration, bronchial epithelium damage, and airway hyperreactivity (AHR), which result from pathogenic Th2-type immune responses to environmental allergens, such as house dust mites (HDM; Dermatophagoides sp.)[Nat Med 18:716-725 (2012)]. Hypersensitivity to HDM is one of the most common allergic responses [Curr Opin Allergy Clin Immunol 9:128-135 (2009)] and >50% of children and adolescents with asthma are sensitized to HDM. Although allergen-specific CD4+ Th2 cells orchestrate the HDM allergic response through their induction of IgE directed against mite allergens, activation of innate immune responses, such as by dendritic cells (DCs) in the airway mucosa, also plays a critical role in HDM-induced allergic inflammation [Allergy Asthma Immunol Res 5:68-74 (2013)]. We have investigated the effects of LTh(αK) in an allergic asthma murine model and its involvement in the maturation and function of DCs. Our results showed that intranasal administration of LTh(αK) or LTh(αK) in combination with HDM allergen, decreased AHR, and attenuated the cardinal features of allergen-induced airway inflammation. In addition, LTh(αK)/HDM also induced allergen specific IgA. These LTh(αK) effects may have resulted from modifying DCs functions to reverse allergic immune responses, as shown by our in vivo and in vitro results. Thus, a detoxified mutant form of LT, LTh(αK), may have clinical applications for allergy and asthma as an immune-modulator. Treatment of allergy-Symptomatic treatment ♦Currently the preferred treatment ♦Attenuate symptoms with anti-histamines, steroid nasal sprays and anti-leukotrienes ♦Most effective for patients with mild allergy symptoms ♦No curative effect   Treatment of allergy-Immunotherapy treats the underlying cause of the allergy ♦Immunotherapy with allergen ♦Anti-IgE antibody (Xolair) ♦Immune-modulator(CpG, CTB, LTh(αK))   •LTh(αK) alleviated airway hyper-responsiveness, airway inflammation and mucus hyper-secretion in der p-induced asthma murine model. •LTh(αK) pretreatment down regulated MHC class II expression of Der p-induced BMDCs from Der p-sensitized mice. •LTh(αK) pretreatment inhibited IL-6 secretion of Der p or LPS-induced BMDCs from Der p-sensitized mice..

The invasion mechanism of the new coronavirus (SARS-CoV-2) is similar to that of SARS in 2003. Recent studies have proposed that "nasal epithelial cells may be the initial point of entry for SARS-CoV-2 infections", an article in "Nature Medicine" pointed out that the goblet cells and ciliated cells in human nasal epithelial cells are likely to be the initial infection point of SARS-CoV-2 and are highly related to immune initiation (https://www.nature.com/articles/s41392 -021-00591-7). If we can administer appropriate drugs into the nasal cavity to the patients, would help protect the mucosa(mouth, nose, or eyes), have effects of early treatment, and prevent transmission. The COVID-19 immunotherapy drug AD17002-SC, its immune modulation and anti-inflammatory properties could prove to be a safe and effective prophylactic treatment of SARS-CoV-2 and a therapeutic treatment of COVID-19. Its safety and effectiveness have already been established in previous studies as an adjuvant therapy intranasally administered with a trivalent inactivated influenza vaccine (Pan et al. 2019; Pan et al. 2020) as well as a single agent for allergic rhinitis (in reporting). The immunopharmaceutical profile supports AD17002-SC as a treatment for COVID-19 both prophylactically and therapeutically. As an immunomodulator, AD17002-SC enhanced the expression of Type I IFN from epithelial cells (Lin et al. 2014; Kuo et al. 2020). Type I IFN is known to initiate innate immunity to prevent viral infection in uninfected cells and defending virus in infected cells. The recent nonclinical study showed that AD17002-SC used to treat SARS CoV-2-induced COVID 19 in hamsters was able to improve the histopathological scores and SARS CoV-2-induced pneumonia. Phase IIa of the human clinical trial, AD17002-SC treats patients with mild cases of COVID-19, was approved by Taiwan Food and Drug Administration (TFDA) and will be implemented in 2021.

The R&D team is engaged in the research and development of a multi-new bacterial project, which is applied to the animal experiment of Haemophilus influenza type b (Hib) and pneumonia vaccine, LTh(αK) conjugated to pneumoniae polysaccharide antigen (S. pneumoniae polysaccharide) It has also been confirmed that it can significantly promote the production of IgG antibodies against polysaccharide antigens. Most commercially available products use tetanus toxoid or diphtheria toxoid as the carrier protein for carbohydrate antigens (carrying protein), but tetanus toxoid or diphtheria toxoid is routinely vaccinated for children. If the two proteins are used for vaccine conjugation, it will cause children to suffer in a short period of time. Too much internal vaccination of these two antigens may cause immune interference and affect immune function. The adverse results in this regard have been confirmed and have been published in the literature. Using genetic engineering methods to transform LT into non-toxic LT(αK) recombinant protein, without chemical detoxification, it can replace tetanus toxoid or diphtheria toxoid as carrier protein. (Currently, only CRM197 (diphtheria toxin) from Wyeth Pharmaceuticals is a genetically modified non-toxic recombinant protein on the market. Others require chemical detoxification before use. Tetanus and diphtheria toxoid are complex to produce and prepare, and LTh(αK) can be used. . coli is mass-produced, the purification process is simple, and the cost is competitive. This plan has been confirmed by experiments that using LTh(αK) as a carrying protein is more effective than current products and does not interfere with tetanus toxoid or diphtheria toxoid as a routine vaccination plan for children. Therefore, this plan is conducive to product competitiveness.