Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.
Adaptive Immunity ; Adjuvants, Immunologic ; Communicable Diseases* ; Humans ; Immunity, Innate ; Vaccine Potency ; Vaccines

Poria is an important medical herb in clinic. The authors isolated a polysaccharide(PCP-Ⅰ) from Poria in previous studies, which is composed of galactose, mannose, fucose and glucose. PCP-Ⅰ exhibited significant adjuvant effects on H1N1 influenza vaccine, hepatitis B surface antigen and anthrax protective antigen, and its adjuvant activity was stronger than aluminium adjuvant. However, little is known about the chemical structure of PCP-Ⅰ at present. In this study, weak acid hydrolysis was used to obtain the backbone oligosaccharide of PCP-Ⅰ. Then periodate oxidation, Smith degradation, methylation analysis, Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance(NMR) and gas chromatography-mass spectrometry(GC-MS) were performed to investigate the chemical structural features of PCP-Ⅰ and its hydrolytic oligosaccharide(PCP-Ⅰ-hy-1). These results suggested that the backbone of PCP-Ⅰ was composed of galactose with α anomeric carbon and β anomeric carbon. The linking residues of galactan are(1→),(l→6) and(1→2,6).
Adjuvants, Vaccine ; Poria ; Hydrolysis ; Spectroscopy, Fourier Transform Infrared ; Galactose ; Influenza A Virus, H1N1 Subtype ; Polysaccharides/chemistry* ; Oligosaccharides ; Carbon

OBJECTIVETo study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine.

METHODSFour batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay.

RESULTSThe GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant.

CONCLUSIONAluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

Adjuvants, Immunologic ; pharmacology ; Aluminum Hydroxide ; pharmacology ; Animals ; Antibodies, Viral ; blood ; Female ; Immunization Schedule ; Male ; Poliovirus Vaccine, Oral ; immunology ; Rats ; Rats, Wistar

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

OBJECTIVETo evaluate the effect and safety of BCG vaccine on initially treated pulmonary tuberculosis and its controlling effect on multidrug-resistant tuberculosis.

METHODSAll 360 volunteers with initially treated pulmonary tuberculosis of positive smear and culture were divided into immunotherapy group (180 cases, also BCG group) and control group (180 cases) at random pair. The patients in BCG group were treated with chemotherapy of a regimen of 2HRZ/2HR and immunotherapy with BCG for 4 months,and the first BCG vaccine was given a month after chemotherapy. Meanwhile, the patients in the control group were treated with chemotherapy of 2HRZ/4HR only.

RESULTS(1) The negative conversion rate of sputum smear in BCG group was 98.3% (177/180), and it was 97.2% (175/180) in control group. There was no significant difference between the two groups both at the ends of 4 and 6 months after treatment (chi2 = 0.1278, P > 0.05). (2) The positive conversion rate of sputum smear in BCG group was 2.3% (4/177), and it was 6.9% (12/175) in control group followed up for 5 years. The successful rate was 96.1% (173/180) in BCG group, and it was significantly higher than that of 90.6% (163/180) in control group (chi2 = 4.4643, P < 0.05). (3) In the 5-year follow up, bacteriologic result was similar to that of X-ray. (4) The occurrence rate of multidrug-resistant tuberculosis was 2.3% (4/177) in BCG group,significantly lower than that of 7.3% (13/178) in the control group (chi2 = 4.9513, P < 0.05).

CONCLUSIONAs an adjunct chemotherapy,immunotherapy with BCG vaccine should be helpful for patients with initially treated pulmonary tuberculosis. It would further strengthen the effects of chemotherapy and reduce the occurrence rate of multidrug-resistant tuberculosis.

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Aged ; Antitubercular Agents ; therapeutic use ; BCG Vaccine ; therapeutic use ; Child ; Female ; Follow-Up Studies ; Humans ; Immunotherapy, Active ; Male ; Middle Aged ; Tuberculosis, Multidrug-Resistant ; prevention & control ; Tuberculosis, Pulmonary ; therapy

Recombinant Fl-V (rFl-V) fusion protein is the main ingredient of the current candidate vaccine against Yersinia pestis infection, which has been under investigation in clinical trial in USA. We investigated the soluble expression conditions of rF1-V in Escherichia coli BL21 (DE3) that we constructed before. After scale-up and optimization of fermentation processes, we got the optimized fermentation process parameters: the culture was induced at the middle exponential phase with 50 µmol/L of IPTG at 25 °C for 5 h. Soluble rFl-V protein was isolated to 99% purity by ammonium sulfate precipitation, ion exchange chromatography, hydrophobic chromatography and gel filter chromatography. The protein recovery was above 20%. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing. Results of purity, quality and western blotting analysis indicated that the target protein is a consistent and properly folded product. Furthermore, the immunogenicity of various antigens formulated with aluminum hydroxide adjuvant was evaluated in mice. Serum antibody titers of 4 groups including 20 µg rFl, rV and rFl-V and 10 µg rFl+10 µg rV, were assayed by ELISA after 2 doses. The antibody titers of anti-Fl with 20 µg rFl-V were obviously higher than titers with other groups; meanwhile there were no significant difference of anti-V antibody titers among them. These findings confirm that rFl-V would be the active pharmaceutical ingredient of the plague subunit vaccine.
Adjuvants, Immunologic ; Animals ; Antibodies, Bacterial ; blood ; Antibody Formation ; Antigens, Bacterial ; immunology ; Blotting, Western ; Chromatography, Ion Exchange ; Enzyme-Linked Immunosorbent Assay ; Mice ; Plague ; prevention & control ; Plague Vaccine ; immunology ; Recombinant Fusion Proteins ; immunology ; Vaccines, Subunit ; immunology ; Yersinia pestis

Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12- IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centres to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised.
Adjuvants, Immunologic ; adverse effects ; therapeutic use ; BCG Vaccine ; adverse effects ; immunology ; therapeutic use ; Humans ; Immunologic Deficiency Syndromes ; diagnosis ; immunology ; Infant, Newborn ; Mycobacterium Infections ; prevention & control ; Mycobacterium bovis ; drug effects ; Neonatal Screening ; methods ; Risk Assessment ; Vaccination ; adverse effects ; methods

OBJECTIVETo investigate the antitumor effect of recombinant IFN-alpha-2b-BCG on mouse bladder cancer MB49 cells in vitro, and to explore its antitumor mechanisms.

METHODSMB49 cells were co-cultured with recombinant BCG or wild BCG, and than were examined by light and transmission electron microscopy. The cell growth was assessed by MTT assay, and apoptosis rate and MHC-I of the MB49 cells was detected by flow cytometry using AO and Hoechst33258 fluorescence immunostaining.

RESULTSThe hIFN-alpha-2b-BCG-treated tumor cells showed slow growth, detachment of some cells, and various degree of degeneration. Light microscopy revealed organelle disorganization, chromatin aggregation, nuclear pyknosis, and cytolysis in some cells. Cellular membrane bulged and some bubbles were seen under fluorescence microscope using AO staining. Hoechst33258 assay also depicted frequent apoptosis in the tumor cells. The MTT assay showed that rBCG more actively than the wild BCG inhibited the proliferation of MB49 cells. The apoptosis rate of the recombinant BCG group was 19.7% and 46.6% at the time point of 24 h and 48 h, respectively, significantly higher than 10.8% and 20.9%, respectively, in the wild BCG group. The results of flow cytometry indicated that both types of BCG enhanced the expression of MHC-I in the MB49 cells, but more effective in the recombinant BCG group.

CONCLUSIONThe recombinant hIFN-alpha-2b-BCG has more strong immuno-modulatory properties, anti-tumor effect on MB49 cells and induces apparent cytotoxicity in the bladder cancer cells in vitro.

Adjuvants, Immunologic ; pharmacology ; Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; BCG Vaccine ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cytotoxicity, Immunologic ; Histocompatibility Antigens Class I ; metabolism ; Interferon-alpha ; pharmacology ; Mice ; Recombinant Proteins ; pharmacology ; Urinary Bladder Neoplasms ; metabolism ; pathology

INTRODUCTION: Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes. METHODS: Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS). RESULTS: At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression. CONCLUSION Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.
Adjuvants, Immunologic/therapeutic use* ; Administration, Intravesical ; BCG Vaccine/therapeutic use* ; Diabetes Mellitus ; Disease Progression ; Humans ; Male ; Metformin/therapeutic use* ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy*

The objective of this study was to evaluate the risk of recurrence in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) after intravesical instillation with chemotherapeutic agents or Bacillus Calmette-Guerin (BCG) therapy. A cohort of 746 patients with intermediate-risk NMIBC comprised the study group. The primary outcome was time to first recurrence. The recurrence rates of the transurethral resection (TUR) alone, chemotherapy, and BCG groups were determined using Kaplan-Meier analysis. Risk factors for recurrence were identified using Cox regression analysis. In total, 507 patients (68.1%), 78 patients (10.5%), and 160 (21.4%) underwent TUR, TUR+BCG, or TUR+chemotherapy, respectively. After a median follow-up period of 51.7 months (interquartile range=33.1-77.8 months), 286 patients (38.5%) developed tumor recurrence. The 5-yr recurrence rates for the TUR, chemotherapy, and BCG groups were 53.6%+/-2.7%, 30.8%+/-5.7%, and 33.6%+/-4.7%, respectively (P<0.001). Chemotherapy and BCG treatment were found to be predictors of reduced recurrence. Cox-regression analysis showed that TUR+BCG did not differ from TUR+chemotherapy in terms of recurrence risk. Adjuvant intravesical instillation is an effective prophylactic that prevents tumor recurrence in intermediate-risk NMIBC patients following TUR. In addition, both chemotherapeutic agents and BCG demonstrate comparable efficacies for preventing recurrence.
Adjuvants, Immunologic/*therapeutic use ; Administration, Intravesical ; Antineoplastic Agents/*therapeutic use ; BCG Vaccine/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Neoplasm Staging ; Risk ; Treatment Outcome ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/*drug therapy/pathology/surgery