AIM: The incorporation of hepatitis B virus (HBV) preS1 region into epitope-based vaccines against HBV has been accepted widely, but the incorporate site and size of preS1 sequence is controversial. Therefore our purp...AIM: The incorporation of hepatitis B virus (HBV) preS1 region into epitope-based vaccines against HBV has been accepted widely, but the incorporate site and size of preS1 sequence is controversial. Therefore our purpose was to further investigate its immunogenic domains for the epitopebased hepatitis B vaccine design.METHODS: Eight GST fusion proteins containing overlapping preS1 fragments in preS1 (21-119) region were expressed in E.coli. Using these purified fusion proteins, the immunogenic domains in preS1 region were identified in detail in mice and humans by Western blot analysis and ELISA.RESULTS: The results in mice showed that the immunogenic domains mainly existed in preS1 (21-59) and preS1 (95-109). Similarly, these fragments had strong immunogenicity in humans; whereas the other parts except for preS1 (60-70) also had some immunogenicity.More importantly, a major immunogenic domain, preS1 (34-59), which has much stronger immunogenicity, was identified. Additionally, the antibodies against some preS1 fragments, especially preS1 (34-59), were speculated to be virus-neutralizing.CONCLUSION: Eight GST fusion proteins containing overlapping preS1 fragments were prepared successfully. They were used for the study on the immunogenic domains in preS1 (21-119) region. The preS1 (34-59) fragments were the major immunogenic domains in the preS1 region, and the antibodies against these fragments were speculated to be virus-neutralizing. Therefore, the incorporation of preS1 (34-59) fragments into epitopebased HBV vaccines may be efficient for enhancement of immune response. Additionally, the results also imply that there are more complex immune responses to preS1 region and more abundant immunogenic domains in humans.展开更多
AIM: To establish the safety and efficacy of an indigenously developed r-hepatitis B vaccine using an accelerated schedule and to highlight the social awareness and commitment in preventing the spreading of hepatitis ...AIM: To establish the safety and efficacy of an indigenously developed r-hepatitis B vaccine using an accelerated schedule and to highlight the social awareness and commitment in preventing the spreading of hepatitis B virus infection. METHODS: The study was a multicentric, double blind, randomized (3:1) study using three doses of vaccine immunization schedule (20μg for those above 10 years old and 10 μg for those below 10 years old) on d 0, 30 and 60. One hundred and sixty-six subjects were enrolled (87 males and 76 females aged 5-35 years). The main outcome measure was assessment of immunogenicity and safety. RESULTS: A 100% seroconversion response was observed on the 30th d after the 1st injection in both the experimental groups. The sero-protection data reported a 41.2-65.6% response on the 30th d after the 1st injection and reached 100% on the 60th d. Descriptive statistical analysis showed a geometric mean titer value of 13.77 mIU/mL in the test (BEVAC) group and 10.95 mlU/mL in the commercial control (ENGERIX-B) group on the 30th d after the 1st injection. The response on the 60th d showed a geometric mean titre value (GMT) of 519.84 mlU/mL in the BEVAC group and 475.46 mlU/mL in the ENGERIX-B group. On the 90th d, the antibody titer response was observed to be 2627.58 mlU/mL in the BEVAC group and 2272.72 mlU/mL in the ENGERIX-B group. Two subjects in each group experienced pains at injection site after the first vaccination. A total of six subjects in both groups experienced a solicited adverse reaction, which included pains, swelling and redness at the injection site, three subjects in the group-B had a pain at the injection site after the third dose. No other serious adverse events occurred and no dose-related local or general symptoms were observed during the study. CONCLUSION: The vaccine is safe, efficacious and immunogenic in comparison with the well documented ENGERIX-B.展开更多
The characteristics of a bacterium strain M3, isolated from cultured flounder Paralichthys olivaceus with remarkable external sign of skin ulcer during an epizootic outbreak, indicated that the bacterium belonged to t...The characteristics of a bacterium strain M3, isolated from cultured flounder Paralichthys olivaceus with remarkable external sign of skin ulcer during an epizootic outbreak, indicated that the bacterium belonged to the species Vibrio anguillarum . Challenge by I.M. (intramuscular injection), bath, and oral administration with M3 showed that it was highly pathogenic for Paralichthys olivacues . The LD 50 dose was 5.144×10 3 CFU/ per fish infection by I.M. injection. Recovered inoculated bacteria from the surviving fish revealed that the asymptomatic carriers could be a latent contagious source. Study of the effect of bacterial culture CFS (cell free supernatant) showed that the exotoxins produced by M3 play an important role in its pathogenicity for flounder. The resistance of M3 to 36 out of 41 antibiotics indicated that the bacterial disease outbreak was mainly attributable to the frequent and excessive use of antimicrobial agents; and that vaccination would be an effective precaution against bacterial disease.展开更多
Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in o...Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.展开更多
Porcine reproductive and respiratory syndrome （PRRS） is the severest disease of pigs worldwide, caused by a highly genetically diverse RNA virus, called Porcine reproductive and respiratory syndrome virus （PRRSV）....Porcine reproductive and respiratory syndrome （PRRS） is the severest disease of pigs worldwide, caused by a highly genetically diverse RNA virus, called Porcine reproductive and respiratory syndrome virus （PRRSV）. The research summarized the genome characteristics of PRRSV particles and the most updated knowledge of structure protein function, and introduced the intellectual of PRRSV transmission and host immune response, which is very important for prevention and control for PRRS. A report showed that mass vaccination can stabilize the immunity of the entire herd, and this is the first required step for a PRRS eradication plan. However, the attenuated live vaccines may not achieve a valid prevention. The final goal of the EU project is to develop new generation, efficacious and safe maker vaccines that can be adapted to temporary changes and geographical differences.Robinson reported that broadly antibodies could neutralize all rapidly evolving type Ⅰ and type Ⅱ viruses, while further studies are expected to elucidate mechanisms of neutralizing antibody production and maturation and to investigate conserved epitope targets of cross-neutralization in this rapidly evolving virus.展开更多
The present study deals with the co-ordination of cytokine （IL-4 and IFN-7） expression and kinetics of peste des petits ruminants （PPR） virus antigen and antibody in PPRV infected and vaccinated goats. The infecte...The present study deals with the co-ordination of cytokine （IL-4 and IFN-7） expression and kinetics of peste des petits ruminants （PPR） virus antigen and antibody in PPRV infected and vaccinated goats. The infected animals exhibited mixed cytokine （both TH1 and TH2） responses in the initial phase of the disease. The infected and dead goats had increased IFN-T response before their death; while IL-4 remained at the base level. The cytokine expression in recovered animals was almost similar to that of vaccinated ones, where a unique biphasic response of IL-4 expression was observed with an up-regulation of IFN-T on 7th days post vaccination （dpv）. Analysis of PPR virus antigen and antibody kinetics in different components of blood from infected and vaccinated animais revealed that the PPR virus antigen load was highest in plasma followed by serum and blood of the infected animals, whereas vaccinated animals showed only marginal positivity on 9th dpv. The antibody titer was high in serum followed by plasma and blood in both vaccinated and infected animals. Therefore, it is inferred that the presence of antigen and antibody were significant with the expression of cytokine, and that a decreased response of IL-4 was noticed during intermediate phase of the disease i.e., 7 to 12m days post infection （dpi）. This indicates the ability to mount a functional TH2 response after 14th dpi could be a critical determinant in deciding the survival of the PPR infected animal.展开更多
The poliomyelitis is an acute infection produced by the polio virus that affects the human central nervous system. It is transmitted by fecal-oral and respiratory contact.There are two types of vaccine, OPV （live att...The poliomyelitis is an acute infection produced by the polio virus that affects the human central nervous system. It is transmitted by fecal-oral and respiratory contact.There are two types of vaccine, OPV （live attenuated virus） and IPV （inactivated polio virus）. Currently, there is a plan of vaccination until the age of 5 with OPV. The children vaccinated expel a virus （derived from the vaccine） to the environment, and some of the people that have oral contact with them, get vaccinated by the herd behavior. Nevertheless, taking into account the lately observed facts about the reversion to virulence of the oral polio vaccine during its circulation in the environment, a change in the current vaccination schedule is being contemplated, where the oral polio vaccine can be replaced by the inactivated vaccine. Nowadays, In Colombia the inactivated oral polio vaccine is recommended for children presenting immune deficiency who are vaccinated with IPV. These children do not expel poliovirus to the environment. This work presents a mathematical model that describes the dynamics of the infection in a population where the two types of vaccination are carried out. The population is divided into two groups of age and Michaelis-Menten interactions. Different strategies of vaccination are simulated and analyzed.展开更多
AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4...AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C.METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series.RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P＜0.05).Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P＜0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity.CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provideprotection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.展开更多
文摘AIM: The incorporation of hepatitis B virus (HBV) preS1 region into epitope-based vaccines against HBV has been accepted widely, but the incorporate site and size of preS1 sequence is controversial. Therefore our purpose was to further investigate its immunogenic domains for the epitopebased hepatitis B vaccine design.METHODS: Eight GST fusion proteins containing overlapping preS1 fragments in preS1 (21-119) region were expressed in E.coli. Using these purified fusion proteins, the immunogenic domains in preS1 region were identified in detail in mice and humans by Western blot analysis and ELISA.RESULTS: The results in mice showed that the immunogenic domains mainly existed in preS1 (21-59) and preS1 (95-109). Similarly, these fragments had strong immunogenicity in humans; whereas the other parts except for preS1 (60-70) also had some immunogenicity.More importantly, a major immunogenic domain, preS1 (34-59), which has much stronger immunogenicity, was identified. Additionally, the antibodies against some preS1 fragments, especially preS1 (34-59), were speculated to be virus-neutralizing.CONCLUSION: Eight GST fusion proteins containing overlapping preS1 fragments were prepared successfully. They were used for the study on the immunogenic domains in preS1 (21-119) region. The preS1 (34-59) fragments were the major immunogenic domains in the preS1 region, and the antibodies against these fragments were speculated to be virus-neutralizing. Therefore, the incorporation of preS1 (34-59) fragments into epitopebased HBV vaccines may be efficient for enhancement of immune response. Additionally, the results also imply that there are more complex immune responses to preS1 region and more abundant immunogenic domains in humans.
基金Supported by the Biological E Limited, Hyderabad, India
文摘AIM: To establish the safety and efficacy of an indigenously developed r-hepatitis B vaccine using an accelerated schedule and to highlight the social awareness and commitment in preventing the spreading of hepatitis B virus infection. METHODS: The study was a multicentric, double blind, randomized (3:1) study using three doses of vaccine immunization schedule (20μg for those above 10 years old and 10 μg for those below 10 years old) on d 0, 30 and 60. One hundred and sixty-six subjects were enrolled (87 males and 76 females aged 5-35 years). The main outcome measure was assessment of immunogenicity and safety. RESULTS: A 100% seroconversion response was observed on the 30th d after the 1st injection in both the experimental groups. The sero-protection data reported a 41.2-65.6% response on the 30th d after the 1st injection and reached 100% on the 60th d. Descriptive statistical analysis showed a geometric mean titer value of 13.77 mIU/mL in the test (BEVAC) group and 10.95 mlU/mL in the commercial control (ENGERIX-B) group on the 30th d after the 1st injection. The response on the 60th d showed a geometric mean titre value (GMT) of 519.84 mlU/mL in the BEVAC group and 475.46 mlU/mL in the ENGERIX-B group. On the 90th d, the antibody titer response was observed to be 2627.58 mlU/mL in the BEVAC group and 2272.72 mlU/mL in the ENGERIX-B group. Two subjects in each group experienced pains at injection site after the first vaccination. A total of six subjects in both groups experienced a solicited adverse reaction, which included pains, swelling and redness at the injection site, three subjects in the group-B had a pain at the injection site after the third dose. No other serious adverse events occurred and no dose-related local or general symptoms were observed during the study. CONCLUSION: The vaccine is safe, efficacious and immunogenic in comparison with the well documented ENGERIX-B.
文摘The characteristics of a bacterium strain M3, isolated from cultured flounder Paralichthys olivaceus with remarkable external sign of skin ulcer during an epizootic outbreak, indicated that the bacterium belonged to the species Vibrio anguillarum . Challenge by I.M. (intramuscular injection), bath, and oral administration with M3 showed that it was highly pathogenic for Paralichthys olivacues . The LD 50 dose was 5.144×10 3 CFU/ per fish infection by I.M. injection. Recovered inoculated bacteria from the surviving fish revealed that the asymptomatic carriers could be a latent contagious source. Study of the effect of bacterial culture CFS (cell free supernatant) showed that the exotoxins produced by M3 play an important role in its pathogenicity for flounder. The resistance of M3 to 36 out of 41 antibiotics indicated that the bacterial disease outbreak was mainly attributable to the frequent and excessive use of antimicrobial agents; and that vaccination would be an effective precaution against bacterial disease.
基金the Deutsche Forschungsgemeinschaft(TRR60 and GK 1045/2)National Major Science and Technology Project for Infectious Diseases of China(2008ZX10002-011,2012ZX10004503)+1 种基金the National Natural Science Foundation of China(No.30271170,30571646,81101248)the International Science&Technology CooperationProgram of China(2011DFA31030)for supporting some of the work in the review
文摘Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.
基金Supported by the Natural Science Research Subject of Minhang Center(2015MHZ041)
文摘Porcine reproductive and respiratory syndrome （PRRS） is the severest disease of pigs worldwide, caused by a highly genetically diverse RNA virus, called Porcine reproductive and respiratory syndrome virus （PRRSV）. The research summarized the genome characteristics of PRRSV particles and the most updated knowledge of structure protein function, and introduced the intellectual of PRRSV transmission and host immune response, which is very important for prevention and control for PRRS. A report showed that mass vaccination can stabilize the immunity of the entire herd, and this is the first required step for a PRRS eradication plan. However, the attenuated live vaccines may not achieve a valid prevention. The final goal of the EU project is to develop new generation, efficacious and safe maker vaccines that can be adapted to temporary changes and geographical differences.Robinson reported that broadly antibodies could neutralize all rapidly evolving type Ⅰ and type Ⅱ viruses, while further studies are expected to elucidate mechanisms of neutralizing antibody production and maturation and to investigate conserved epitope targets of cross-neutralization in this rapidly evolving virus.
文摘The present study deals with the co-ordination of cytokine （IL-4 and IFN-7） expression and kinetics of peste des petits ruminants （PPR） virus antigen and antibody in PPRV infected and vaccinated goats. The infected animals exhibited mixed cytokine （both TH1 and TH2） responses in the initial phase of the disease. The infected and dead goats had increased IFN-T response before their death; while IL-4 remained at the base level. The cytokine expression in recovered animals was almost similar to that of vaccinated ones, where a unique biphasic response of IL-4 expression was observed with an up-regulation of IFN-T on 7th days post vaccination （dpv）. Analysis of PPR virus antigen and antibody kinetics in different components of blood from infected and vaccinated animais revealed that the PPR virus antigen load was highest in plasma followed by serum and blood of the infected animals, whereas vaccinated animals showed only marginal positivity on 9th dpv. The antibody titer was high in serum followed by plasma and blood in both vaccinated and infected animals. Therefore, it is inferred that the presence of antigen and antibody were significant with the expression of cytokine, and that a decreased response of IL-4 was noticed during intermediate phase of the disease i.e., 7 to 12m days post infection （dpi）. This indicates the ability to mount a functional TH2 response after 14th dpi could be a critical determinant in deciding the survival of the PPR infected animal.
文摘The poliomyelitis is an acute infection produced by the polio virus that affects the human central nervous system. It is transmitted by fecal-oral and respiratory contact.There are two types of vaccine, OPV （live attenuated virus） and IPV （inactivated polio virus）. Currently, there is a plan of vaccination until the age of 5 with OPV. The children vaccinated expel a virus （derived from the vaccine） to the environment, and some of the people that have oral contact with them, get vaccinated by the herd behavior. Nevertheless, taking into account the lately observed facts about the reversion to virulence of the oral polio vaccine during its circulation in the environment, a change in the current vaccination schedule is being contemplated, where the oral polio vaccine can be replaced by the inactivated vaccine. Nowadays, In Colombia the inactivated oral polio vaccine is recommended for children presenting immune deficiency who are vaccinated with IPV. These children do not expel poliovirus to the environment. This work presents a mathematical model that describes the dynamics of the infection in a population where the two types of vaccination are carried out. The population is divided into two groups of age and Michaelis-Menten interactions. Different strategies of vaccination are simulated and analyzed.
文摘AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C.METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series.RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P＜0.05).Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P＜0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity.CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provideprotection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.
