The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.
Adaptive Immunity ; Antigens, Viral/immunology ; *Cross Protection ; Genome, Viral ; Humans ; Immunity, Innate ; Influenza Vaccines/*immunology/therapeutic use ; Influenza, Human/*prevention & control ; Orthomyxoviridae/genetics/immunology ; Vaccines, Attenuated

Recombinant baculoviruses containing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein gene of the viscerotropic velogenic (vv) Newcastle disease virus (NDV) isolate, Kr-005/00, and a lentogenic La Sota strain of the NDV were constructed in an attempt to develop an effective subunit vaccine to the recent epizootic vvNDV. The level of protection was determined by evaluating the clinical signs, mortality, and virus shedding from the oropharynx and cloaca of chickens after a challenge with vvNDV Kr-005/00. The recombinant ND F (rND F) and recombinant HN (rND HN) glycoproteins derived from the velogenic strain provided good protection against the clinical signs and mortality, showing a 0.00 PI value and 100% protection after a booster immunization. On the other hand, the combined rND F + HN glycoprotein derived from the velogenic strain induced complete protection (0.00 PI value and 100% protection) and significantly reduced the amount of virus shedding even after a single immunization. The rND F and rND HN glycoproteins derived from the velogenic strain had a slightly, but not significantly, greater protective effect than the lentogenic strain. These results suggest that the combined rND F + HN glycoprotein derived from vvNDV can be an ideal subunit marker vaccine candidate in chickens in a future ND eradication program.
Animals ; Baculoviridae/genetics/*immunology ; Chickens/*virology ; DNA Primers ; Gene Amplification ; HN Protein/genetics/*therapeutic use ; Korea ; Marek Disease/immunology/prevention & control ; Newcastle Disease/immunology/*prevention & control ; Spodoptera/virology ; Vaccines, Synthetic/genetics/therapeutic use ; Viral Vaccines/genetics/therapeutic use

OBJECTIVESTo establish a transplanted tumor producing HCV NS3 protein in mice and study the therapeutic effect of minigene vaccine based on invariant chain substitution.

METHODSSP2/0-NS3 cells expressing HCV NS3 antigen were injected subcutaneously into BALB/ c mice. After three days of inoculation, different therapeutical reagents were injected intramuscularly into different groups of mice. The boost immunization was carried out two weeks after the first immunization. The efficiency of HCV NS3 Th1 minigene vaccine was estimated after 60 days observation.

RESULTSFor saline, pCI-neo, pHCV-NS3 and pHCV-NS3-Th1 treated groups, the induction period needed for tumor growth was 16.17+/-2.55, 14.40+/-1.82, 16.75+/-2.36, and 24.00+/-5.57 days (t =2.623, P =0.034 vs saline, t =3.713, P =0.010 vs pCI-neo and t =2.425, P =0.045 vs pHCV-NS3) respectively. The tumorigenesis rates were 100%, 100%, 57.1% (8/14, chi2 = 6.190, P = 0.013 vs saline and chi2 = 6.608, P = 0.010 vs pCI-neo) and 46.7% (7/15, chi2 = 9.707, P = 0.002 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo ) respectively. The survival rates were 0, 0, 50.0% (7/14, chi2 = 5.787, P = 0.016 vs saline and chi2 = 9.333, P = 0.002 vs pCI-neo) and 53.3% (8/15, chi2 = 6.651, P = 0.010 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo) respectively. The average tumor diameter of the pHCV-NS3-Th1 treated group was significantly smaller compared with the control groups and the pHCV-NS3 treated group (P =0.001). Moreover, the average survival time of tumor-bearing mice immunized with pHCV-NS3-Th1 was 6 days longer compared with the saline treated group, 12 days longer compared with the pCI-neo treated group (P =0.001), and 6 days compared with the pHCV-NS3 treated group.

CONCLUSIONHCV NS3 Th1 epitope vaccine might be a potential biotherapy candidate against HCV infection.

Animals ; Female ; Mice ; Mice, Inbred BALB C ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Transplantation ; Random Allocation ; Tumor Cells, Cultured ; Vaccines, Synthetic ; therapeutic use ; Viral Hepatitis Vaccines ; therapeutic use ; Viral Nonstructural Proteins ; biosynthesis ; genetics

OBJECTIVETo evaluate the incidence of precore mutation in HBeAg negative HBV infected patients and the therapeutic effect of the immune therapy (levamisole + HBV vaccine + dipyridamole) on patients chronically infected by HBV with precore mutation.

METHODSThe precore region of HBV from the HBeAg (-) chronic hepatitis patients was sequenced and the patients suffered from HBV with precore mutation were treated with immune therapy.

RESULTSThe precore mutation rate was 10/12. The therapeutic effect of the immune therapy on the precore mutation patients (5/7) was better than that on the HBsAg(+), HBeAg(+) patients (2/11), P less than 0.05.

CONCLUSIONThe precore mutation rate was quite high in the HBsAg(+), HBeAg(-) patients we studied. The immune-therapy has some therapeutic effects on the patients with precore mutation. But the number of cases was too small, further study is needed.

Adolescent ; Adult ; Child ; Combined Modality Therapy ; DNA, Viral ; blood ; Dipyridamole ; therapeutic use ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; therapy ; virology ; Humans ; Immunotherapy ; Lamivudine ; therapeutic use ; Levamisole ; therapeutic use ; Middle Aged ; Mutation

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10⁶ IU/ml than those with HBV DNA <10⁶ IU/ml (12.2% vs. 1.8%; χ²=11.275, P=0.006), and (24.4% vs. 16.0%, χ²=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10⁶ IU/ml than that of maternal HBV DNA<10⁶ IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>10⁶ IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral ; Female ; Fetal Distress/drug therapy* ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/therapeutic use* ; Hepatitis B virus/genetics* ; Humans ; Immunoglobulins/therapeutic use* ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious

Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV\'s significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping.
DNA, Viral/*analysis ; Early Detection of Cancer/*methods ; Female ; *Genome, Viral ; Genotype ; Humans ; Papillomaviridae/classification/*genetics ; Papillomavirus Infections/complications/drug therapy/*virology ; Papillomavirus Vaccines/therapeutic use ; Uterine Cervical Neoplasms/diagnosis/drug therapy/*virology

OBJECTIVETo evaluate the advantages of combination therapy with interferon-alpha plus nucleoside analogue-lamivudine or HBV vaccine in children with HBeAg positive chronic hepatitis B.

METHODSA total of 120 patients with HBeAg positive chronic hepatitis B were divided into three groups, 40 patients per group. Each group was treated with one of the following therapies respectively: Group A IFN-alpha 1b 10 MU/m2 three times per week (Tiw); Group B IFN-alpha 1b 10MU/m2 three times per week (Tiw) plus lamivudine 3 mg/kg for 6 months. Group C IFN-alpha 1b 10 MU/m2 three times per week (Tiw) plus HBV vaccine 30 microg one a month.

RESULTSThere was no significant difference in normalizing rate of ALT among the three groups at end of treatment. There was more significant difference in negative rate (seroconversion) of serum HBV DNA and HBeAg in group B than group A and group C (P less than 0.05).

CONCLUSIONThe combination therapy of IFN-alpha 1b plus lamivudine seemed to be more effective than the therapy with IFN-alpha alone and the combination of IFN-alpha and HBV vaccine.

Anti-HIV Agents ; therapeutic use ; Child ; Child, Preschool ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B e Antigens ; blood ; genetics ; immunology ; Hepatitis B virus ; drug effects ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Lamivudine ; therapeutic use ; Male ; Treatment Outcome

OBJECTIVETo observe the gene therapeutic effects in vivo using prepared recombinant adenovirus coding for Fas gene with steroid hormone.

METHODSTransplant the keloid tissue into athymic nude mice and then observe the tissue's change after injecting Ad-fas (T) or Ad-Fas (B) followed by steroid hormone.

RESULTS(1) The keloid tissue shrinked slightly when adenovirus was singly injected. (2) The keloid tissue transplanted into athymic nude mice was seen significantly shrink after injection of Ad-Fas (T) or Ad-Fas (B) followed by steroid hormone. (3) The injection of Ad-Fas (T) or Ad-Fas (B) may be helpful to decrease the dose of steroid hormone which may significant depressed its side-effect.

CONCLUSIONS(1) Due to the immune deficiency in nude mice, the conclusion can not be made that the single injection of adenovirus is invalid. (2) Gene therapy in vivo was also successfully completed using the newly built Ad-Fas (T) and Ad-Fas (B). The results were satisfactory. The success in experimental study may pave a sound foundation for further gene therapy in keloid.

Adenoviridae ; genetics ; Animals ; Disease Models, Animal ; Genetic Therapy ; methods ; Genetic Vectors ; Hormones ; therapeutic use ; Keloid ; therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Transfection ; Viral Vaccines ; genetics ; fas Receptor ; genetics

OBJECTIVETo investigate the high expression of HPV16L2N120E7E6 fusion protein by prokaryotic expression system, and evaluate its immunogenicity and antitumor efficacy in vaccinated mice.

METHODSThe HPV16L2N120E7E6 fusion gene, its codons were optimized to increase the expression of the protein, was constructed by overlap extension PCR and inserted into prokaryotic expression vector pET9a. Then the fusion protein was expressed by inducing with IPTG in E. coli strain BL21 (DE3) harboring with plasmid pETL2N120E7E6, and further detected by SDS-PAGE and Western-blot. Finally, the humoral and cellular immune responses were measured by ELISA and ELISPOT, respectively, in vaccinated mice with the purified HPV16L2N120E7E6 fusion protein, and the antitumor efficacy was assessed in mice using the TC-1 tumor challenge model.

RESULTSThe codon-optimized HPV16L2N120E7E6 fusion gene was highly expressed in E. coli strain BL21 (DE3) harboring with plasmid pETL2N120E7E6, and the amount of fusion protein was nearly 48.6% of the total bacterial protein. The purified fusion protein could induce high titer of specific antibody against L2, E7 and E6 in vaccinated mice. When accompanied with the adjuvant CpG, the fusion protein was able to elicit strong and moderate cellular immune responses in vaccinated mice against peptide HPV16E7(49-57) and peptide pools of HPV16E6, respectively. Furthermore, the tumor therapeutic experiment showed that HPV16L2N120E7E6 + CpG could prevent the tumor formation in 80.0% (8/10) vaccinated mice.

CONCLUSIONSThe data of this study suggest that HPV16L2N120E7E6 fusion protein could be a promising candidate vaccine for treatment of chronic HPV16 infection and post-operative adjuvant therapy for cervical cancer.

Adjuvants, Immunologic ; pharmacology ; Animals ; Cancer Vaccines ; immunology ; therapeutic use ; Capsid Proteins ; genetics ; immunology ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Codon ; Escherichia coli ; immunology ; metabolism ; Female ; Humans ; Immunization ; methods ; Immunotherapy ; methods ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Oligodeoxyribonucleotides ; immunology ; Oncogene Proteins, Viral ; genetics ; immunology ; metabolism ; Papillomavirus E7 Proteins ; genetics ; immunology ; metabolism ; Papillomavirus Vaccines ; immunology ; therapeutic use ; Plasmids ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism ; Repressor Proteins ; genetics ; immunology ; metabolism

Adenoviridae ; genetics ; Animals ; Apoptosis ; drug effects ; Carcinoma, Squamous Cell ; genetics ; metabolism ; therapy ; Cell Cycle ; drug effects ; Clinical Trials as Topic ; Genes, p53 ; Genetic Therapy ; Genetic Vectors ; Humans ; Mouth Neoplasms ; genetics ; metabolism ; therapy ; Mutation ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Viral Vaccines ; pharmacology ; therapeutic use