1.Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies.
Shujing WANG ; Huiqin LIU ; Xinyi ZHANG ; Feng QIAN
Protein & Cell 2015;6(7):480-503
Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.
Adjuvants, Immunologic
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pharmacology
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Administration, Intranasal
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Administration, Oral
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Antigens
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administration & dosage
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Drug Delivery Systems
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Humans
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Proteins
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administration & dosage
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Vaccination
2.Innate endogenous adjuvants prime to desirable immune responses via mucosal routes.
Protein & Cell 2015;6(3):170-184
Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing attentions have been paid to mucosal vaccination due to its multiple advantages over conventional ways. Subunit or peptide antigens are more reasonable immunogens for mucosal vaccination than live or attenuated pathogens, however adjuvants are required to augment the immune responses. Many mucosal adjuvants have been developed to prime desirable immune responses to different etiologies. Compared with pathogen derived adjuvants, innate endogenous molecules incorporated into mucosal vaccines demonstrate prominent adjuvanticity and safety. Nowadays, cytokines are broadly used as mucosal adjuvants for participation of signal transduction of immune responses, activation of innate immunity and polarization of adaptive immunity. Desired immune responses are promptly and efficaciously primed on basis of specific interactions between cytokines and corresponding receptors. In addition, some other innate molecules are also identified as potent mucosal adjuvants. This review focuses on innate endogenous mucosal adjuvants, hoping to shed light on the development of mucosal vaccines.
Adjuvants, Immunologic
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Animals
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Humans
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Immunity, Innate
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immunology
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Immunity, Mucosal
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immunology
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Vaccines
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administration & dosage
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immunology
3.Immunomodulators to be applied with good reason.
Xiao-dong ZHAO ; Xi-qiang YANG
Chinese Journal of Pediatrics 2006;44(6):401-402
4.Efficacy of local injection of bacillus calmette-guerin polysaccharide nucleic acid following CO2 laser resection on condyloma acuminatum.
Xiao YU ; Zhangqun YE ; Weimin YANG ; Rongjin DENG
National Journal of Andrology 2004;10(2):117-121
OBJECTIVETo observe the efficacy of local injection of bacillus calmette-guerin polysaccharide-nuclear acid (BCG-PSN) following CO2 laser resection on condyloma acuminatum (CA).
METHODSOne hundred and six patients with CA were randomized into BCG-PSN group (60 cases) and interferon group (46 cases), treated respectively with BCG-PSN local injection and interferon subcutaneous injection following CO2 laser resection and followed up for 3 months.
RESULTSThe healing rate of the BCG-PSN group was 88.3% and that of the interferon group was 71.7%.
CONCLUSIONThe BCG-PSN local injection following CO2 laser resection is effective for CA patients.
Adjuvants, Immunologic ; administration & dosage ; Adult ; Aged ; BCG Vaccine ; administration & dosage ; Condylomata Acuminata ; therapy ; Female ; Humans ; Laser Therapy ; Male ; Middle Aged ; Nucleic Acids ; administration & dosage ; Polysaccharides ; administration & dosage
5.Expert consensus on intravesical therapy for non-muscle invasive bladder cancer (2021 edition).
Chinese Journal of Oncology 2021;43(10):1027-1033
Bladder cancer is one of the common malignant tumors in China, with 75% of bladder cancer being non-muscle invasion with a high recurrence rate after surgery. Intravesical therapy is an useful methods to either directly kill tumor cells by infusing cytotoxic drugs into the bladder or directly or indirectly induce local immune responses of the body through infusing immune agents, such as bacillus calmette guerin, and thus reduce the risk of tumor recurrence and progression. In 2019, the Urological Chinese Oncology Group issued the "Expert consensus on intravesical therapy on non-muscle invasive bladder cancer" . Recently, great progress in the clinical diagnosis and treatment of non-muscle invasive bladder cancer has been achieved domestically and abroad, including the risk assessment of non-muscle invasive bladder cancer, the therapeutic choice of intravesical drugs, the adverse reactions and treatment experience of intravesical therapy, and clinical research on new types of intravesical drugs. This consensus is made according to domestic and overseas evidence-based medicine in combination with current clinical practice and experience of intravesical therapy for non-muscle invasive bladder cancer in China. It is an update of the 2019 expert consensus, with the wish to provide a guidance for domestic clinical standardized intravesical therapy for non-muscle invasive bladder cancer.
Adjuvants, Immunologic/therapeutic use*
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Administration, Intravesical
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Consensus
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Humans
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Neoplasm Invasiveness
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Neoplasm Recurrence, Local/drug therapy*
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Urinary Bladder Neoplasms/drug therapy*
6.Effect of tetanus toxoid powder needleless injection on the concentration of serum antibody IgG in mice.
Jia-Bo WANG ; Xu ZHOU ; Zhe-Wei WANG ; Cheng JIN ; Xiao-He XIAO
Acta Pharmaceutica Sinica 2009;44(12):1406-1409
In this study, a self-designed powder needleless injection system was compared with subcutaneous injection using a needle and syringe to deliver tetanus toxoid (TT) into mice to elicit immunity. First of all, factors influencing the prepartion of TT into powder by being absorbed on aluminium hydroxide were investigated and the micromeritic characters of Al (OH)3-TT powder were observed with optical microscope and laser particle analyzer. The results showed that salt concentration and absorption time had an enhancive effect on drug loading, but the pH value and temperature did not influence the absorption reaction obviously. The absorption reaction was optimized with sodium chloride concentration of 0.4 mol x L(-1) and lasting for 10 min. The average diameter of Al(OH)3-TT powder prepared with conditions optimized above was (60.6 +/- 4.4) microm. The immunization effect of TT was determined through enzyme-linked immunosorbent assay (ELISA) of the concentration of IgG antibody elicited by TT. With delivery of Al(OH)3-TT (of 30 microg TT) by powder needleless injection to mice, the IgG antibody concentration were (6.19 +/- 0.52) and (10.70 +/- 0.78) U x L(-1) after immunization of 4 and 8 weeks, respectively, while the values were (4.25 +/- 0.58) and (7.48 +/- 0.57) U x L(-1) by subcutaneous injection (of 20 microg TT) using a needle and syringe. The results suggested that the self-designed powder needleless injection of Al(OH)3-TT was comparable to subcutaneous injection with a good immunity.
Adjuvants, Immunologic
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administration & dosage
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Aluminum Hydroxide
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administration & dosage
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Animals
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Drug Compounding
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Female
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Immunoglobulin G
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blood
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Injections, Jet
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Male
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Mice
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Particle Size
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Powders
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Tetanus Toxoid
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administration & dosage
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immunology
7.Clinical trial of sequential antiviral therapy for patients with chronic hepatitis B in China.
Chun-liang LEI ; Xiao-mou PENG ; Xiao-ping TANG ; Zhan YANG ; Hui-min FAN ; Xiao-zhen YUAN
Chinese Journal of Experimental and Clinical Virology 2004;18(1):69-72
OBJECTIVETo establish a sequential antiviral regime and evaluate its efficacy in patients with chronic hepatitis B using a controlled trial.
METHODSSeventy-four patients with chronic hepatitis B were divided into 3 groups: 30 cases were enrolled in the sequential antiviral group in which patients received eight-week treatment with thymosin alpha1 (1.6 mg/time, subcutaneous injection, 2 times/week), six-month treatment with interferon (500 MU/ times, muscle inject, every other day) begun in the fifth week of the therapeutic course, and lamivudine treatment (100 mg/days) begun 2 months later after HBeAg seroconversion or just after the withdrawal of interferon to more than eighteen months. Fourteen cases were enrolled in combination group in which patients received six-month treatment with interferon and thymosin alpha1 simultaneously in the same manner as in sequential antiviral group. Thirty cases were enrolled in lamivudine group in which patients received more than eighteen-month treatment with lamivudine.
RESULTSThe temporary rates of HBeAg seroconversion and normalization of alanine aminotransferase (effective rate) in sequential antiviral group, combination group and lamivudine group were 76.7%, 78.6% and 13.3%, respectively. The effective rates of sequential group and combination group were very similar, and significantly higher than that of lamivudine group (P less than 0.01). Long-term efficacy rates were 76.7%, 57.1% and 16.7% among the three groups, respectively. The long-term effective rate of sequential group was relatively higher. The rate of liver damage sensitive period in sequential antiviral group and combination group was 47.7%. The time of onset was from 2 to 8 weeks after the treatment begun, earlier than that from 6 to 8 weeks after the beginning of interferon alone in the literature.
CONCLUSIONSequential antiviral therapy had much higher rates of long-term HBeAg seroconversion, undetectable HBV DNA and normalization of alanine aminotransferase with good cost-effectiveness. Its mechanism to promote the antiviral effect might be dependent on the immunoregulatory action of thymosin alpha1 in the earlier period and the specific inhibition of HBV DNA replication by lamivudine in the later period of the therapeutic course.
Adjuvants, Immunologic ; administration & dosage ; Antiviral Agents ; administration & dosage ; China ; Drug Therapy, Combination ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; Lamivudine ; administration & dosage ; Thymosin ; administration & dosage ; analogs & derivatives ; Treatment Outcome
8.Enhancement of a hepatitis B DNA vaccine potency using aluminum phosphate in mice.
Zeng-wei LIANG ; Hong REN ; Ying-hua LANG ; Yong-guo LI
Chinese Journal of Hepatology 2004;12(2):79-81
OBJECTIVESTo study antibody response to a hepatitis B DNA vaccine by formulation with aluminum phosphate in mice.
METHODSAn eukaryotic expression plasmid inserted HBsAg gene (pcDNA3.1-S) was constructed by cloning technique and the accuracy of the construct was confirmed by restriction enzyme digestion and DNA sequencing, then hepatitis B DNA vaccine formulations were prepared by mixing pcDNA3.1-S with various concentration of aluminum phosphate in 0.9% NaCl. HBsAg expressions were assayed by ELISA in vivo five days after intramuscular injection of pcDNA3.1-S with or without aluminum phosphate. And serum samples were obtained from individual immunized or control mice 6 weeks post injection. Then anti-HBs were assayed in mice sera by ELISA.
RESULTSFive days after intramuscular immunization, the levels of HBsAg expression of groups with aluminum phosphate showed no difference from those of control group in tibialis arterials muscles. In sera, HBsAg could not be detectable in all groups. Intramuscular immunization of BABL/C mice with pcDNA3.1-S mixed aluminum phosphate (0microg, 1microg, 10microg, 50microg, 100microg) 6 weeks later, the P/N values of anti-HBs in sera were 11.54+/-5.60, 11.00+/-6.62, 20.30+/-10.20, 49.18+/-24.40 and 48.68+/-27.78, respectively. It showed that pcDNA3.1-S mixing with aluminum phosphate could increase anti-HBs titers in mice.
CONCLUSIONNo increase of HBsAg expression was observed by mixing plasmid pcDNA3.1-S with various concentration of aluminum phosphate in vivo. But Intramuscular immunization of BALB/C mice with pcDNA3.1-S mixing aluminum phosphate adjuvant can increase anti -HBs titers. It seemed that aluminum phosphate would be valuable for further investigation as a potential adjuvant of hepatitis B DNA vaccines.
Adjuvants, Immunologic ; administration & dosage ; Aluminum Compounds ; administration & dosage ; Animals ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Mice ; Mice, Inbred BALB C ; Phosphates ; administration & dosage ; Vaccines, DNA ; administration & dosage ; immunology
10.A randomized trial comparing cisplatin plus 5-fluorouracil with or without levamisole in operable gastric cancer.
Jong Soo CHOI ; Kyoo Hyung LEE ; Myung Ju AHN ; Jung Shin LEE ; Je Han LEE ; Dae Young ZANG ; Chel Won SUH ; Sang We KIM ; Woo Gun KIM ; Jin Cheon KIM ; SukKoo KIM ; Kun Choon PARK ; Moo Song LEE ; Sang Hee KIM
The Korean Journal of Internal Medicine 1997;12(2):155-162
OBJECTIVES: To determine the effectiveness and toxicity when levamisole was added to the adjuvant combination chemotherapy in patients with operable gastric cancer. METHODS: After en bloc resection of gastric cancer without gross or microscopic evidence of residual disease from April 1991 to December 1992, 100 patients were randomized to 6 months of 5-fluorouracil 1,000 mg/m2/day administered as continuous infusion for 5 days, cisplatin 60 mg/m2/day as intravenous infusion for 1 day with or without levamisole (50 mg every eight hours P.O for a period of three days every 2 weeks for 6 months). This chemotherapy treatment was begun within 2 to 4 weeks after the surgery. The chemotherapy consisted of discrete 5-day courses administered at 4-weeks intervals. All 100 patients are assessable. RESULTS: The fifty patients were assigned to each treatment group. There was no statistical difference and no bias in the distribution of characteristics of the 100 evaluable patients between the two groups. A total of 274 courses of treatment were given in the levamisole group and 260 courses of treatment in non-levamisole group. Eleven patients in each group did not finish planned 6 courses of treatment mainly due to non-compliance. At median follow up of 39 months, 32 patients relapsed 19 in the levamisole group and 13 in the non-levamisole group (p = 0.284). Twenty five patients died of relapsed diseases, 15 in the levamisole group and 10 in the non-levamisole group. The levamisole group tended to show more risk of overall death rate and recurrence than the non-levamisole group. However, this result was not statistically significant at 3 years. The treatment was well tolerated in both treatment groups. The grade 2-3 toxicities were nausea/ vomiting (levamisole, non-levamisole group; 31.7%, 29.3% of treatment courses respectively), diarrhea (7.6%, 8.4%), mucositis (11.6%, 12.3%), and leukopenia (9.8%, 9.6%). CONCLUSION: Levamisole had negative effects on disease-free survival and overall survival when added to adjuvant combination chemotherapy of cisplatin and 5-fluorouracil in patients with operable gastric cancer. Both treatment arms were generally well tolerated and the toxicity profile was similar with or without levamisole.
Adjuvants, Immunologic/administration & dosage*
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Adult
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Aged
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Antineoplastic Agents, Combined/therapeutic use*
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Antineoplastic Agents, Combined/adverse effects
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Cisplatin/administration & dosage
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Comparative Study
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Female
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Fluorouracil/administration & dosage
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Human
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Levamisole/administration & dosage*
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Male
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Middle Age
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Stomach Neoplasms/mortality
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Stomach Neoplasms/drug therapy*