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Vaccine ; 37(36): 5341-5349, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31351798


A suitable animal model of CVA16 infection is crucial in order to understand its pathogenesis and to help develop antiviral vaccines or screen therapeutic drugs. The neonatal mouse model has a short sensitivity period to CA16 infection, which is a major limitation. In this study, we demonstrate that adult (60-day-old) gerbils are susceptible to CVA16 infection at high doses (108.0 TCID50). A clinical isolate strain of CVA16 was inoculated intraperitoneally into adult gerbils, which subsequently developed significant clinical symptoms, including hind limb weakness, paralysis of one or both hind limbs, tremors, and eventual death from neurological disorders. Real-time RT-PCR revealed that viral loads in the spinal cord and brainstem were higher than those in other organs/tissues. Histopathological changes, such as neuronal degeneration, neuronal loss, and neuronophagia, were observed in the spinal cord, brainstem, and heart muscle, along with necrotizing myositis. Gerbils receiving both prime and boost immunizations of alum adjuvant inactivated vaccine exhibited no clinical signs of disease or mortality following challenge by CVA16, whereas 80% of control animals showed obvious clinical signs, including slowness, paralysis of one or both hind limbs, and eventual death, suggesting that the CVA16 vaccine can fully protect gerbils against CVA16 challenge. These results demonstrate that an adult gerbil model provides us with a useful tool for studying the pathogenesis and evaluating antiviral reagents of CVA16 infection. The development of this animal model would also be conducive to screening promising CVA16 vaccine candidates as well as further vaccination evaluation.

Enterovirus/imunologia , Enterovirus/patogenicidade , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , Animais , Animais Recém-Nascidos , Anticorpos Neutralizantes/imunologia , Modelos Animais de Doenças , Feminino , Gerbillinae , Masculino , Carga Viral/imunologia
Am J Transl Res ; 10(5): 1539-1551, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887967


OBJECTIVE: This study aimed to: evaluate long-term toxicity and pharmacokinetic parameters; to identify the target organ of toxicity of a recombinant adenovirus vaccine expressing human papillomavirus 16 E6 and E7 proteins (HPV16 E6E7-Ad5 Vac) in primates; and to determine the specific immune response of this recombinant adenovirus vaccine. METHOD: HPV16 E6E7-Ad5 Vac (dose 4.68 × 109 IU/bottle) was administered to Macaca fascicularis (M. fascicularis) to evaluate its long-term toxicity. The Cynomolgus Monkeys were divided into a negative control group (sodium chloride injection group), a low-dose group (4.68 × 108 IU/macaque), and, a high-dose group (4.68 × 109 IU/macaque). The drugs were administered at intervals of once every three weeks (D1, D21, D42). The macaques were observed until the sixth week of the recovery period (D84) for safety and toxicological indicators and pharmacokinetic indicators. To study the specific immune response in Rhesus Macaque, empty viruses (rAd5-null) and buffer were inoculated as controls, respectively. Two doses of the vaccine were given at 1.0 × 108 IU/ml and 1.0 × 109 IU/ml and theHPV-16 E6-/HPV-16 E7-specific IFN-γ productions were measured. RESULTS: The macaques of both the high-dose group and the low-dose group did not exhibit any systemic toxic response. The administered safe dose of the vaccine was 4.68 × 109 IU per animal. Following vaccination, HPV16 E6/E7-specific antibodies were observed to be generated in both groups, indicating an immune response of the lymphocytes targeting HPV16 E6 and HPV16 E7 epitopes (specific NF-r) was elicited. The peak level of HPV-16 E6-/HPV-16 E7-specific IFN-γ production was observed in the ninth week.

Zhonghua Liu Xing Bing Xue Za Zhi ; 31(12): 1332-5, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21223658


OBJECTIVE: To evaluate the long-term immunogenicity and effectiveness of live attenuated hepatitis A (HA) vaccine (H2 strain) after one dose injection, through a 15 years' follow up observation. METHODS: A total of 220 children with negative anti-HAV antibody (aged 1-3 y) were involved and followed up in Jiaojiang district, Taizhou city, Zhejiang province. Indicators would include seroconversion and geometric mean titer (GMT) levels after inoculation the vaccine with single dose at 2 m, 12 m, 6 years, 10 years and 15 years. Epidemiological observation was carried out within the 15 years to evaluate the relationship between vaccine coverage, the incidence of HA and the overall effectiveness. In the studied population, serum was tested by ELISA (calibrated by WHO international reference) and ABBOTT Axsym HAVAB mEIA. RESULTS: Seroconversion rates were found to be 98.6% and 81.3% after 2 months and 15 years of inoculation and slowly decreased. GMT level was 128 mIU/ml after 15 years, significantly higher than the required protective level of 20 mIU/ml, recommended by WHO experts. Effectiveness through the 15-year follow up program showed a significant correlation between vaccine coverage and incidence of HA in 1-15 years aged group (Kendall-Rank test, τ =-0.931, P<0.01). There was no HA case seen among the observed accumulated 236 413 person-year vaccines, compared to 4 HA cases discovered in the 27 206 person-year of the non-vaccinees. The overall protective rate reached 100%. Through a mass vaccination program on children, the whole population established an immune-defence to enable the incidence of HA decreased by 96.7%. CONCLUSION: The long-term immunogenicity and effectiveness of live attenuated hepatitis A vaccine (H2 strain) after one dose injection could last as long as 15 years.

Vacinas contra Hepatite A , Hepatite A/imunologia , Hepatite A/prevenção & controle , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hepatite A/epidemiologia , Vacinas contra Hepatite A/imunologia , Humanos , Incidência , Lactente , Masculino , Vacinação em Massa , Vacinas Atenuadas/imunologia
Chin Med J (Engl) ; 118(22): 1851-6, 2005 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-16313838


BACKGROUND: Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization. METHODS: A total of 220 children with negative anti-HAV antibody (aged 1 - 3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre (GMT) level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay. RESULTS: Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years. CONCLUSIONS: Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination.

Vacinas contra Hepatite A/imunologia , Hepatite A/prevenção & controle , Vacinação em Massa , Adolescente , Adulto , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Seguimentos , Anticorpos Anti-Hepatite/sangue , Humanos , Imunoglobulina G/sangue , Vacinas Atenuadas/imunologia
Rapid Commun Mass Spectrom ; 19(6): 838-42, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15723442


A method was developed for quantitative determination of deuterium incorporated into live organisms or biological macromolecules. The deuterated biological material was mixed with a bovine serum albumin (BSA) supporter to make a homogeneous sample for which the deltaD value (vs. VSMOW) was analyzed using a dual-inlet gas isotope mass spectrometer. The method is described in detail, and the equation for calculation of deuterium content is presented, i.e., CbioD=1/500 x k x RVSMOW x CBSAH x 10(6) ppm. Deuterated hepatitis A virus (HAV) RNA and BSA were systematically investigated. The results demonstrate that the method is capable of direct measurement of deuterium content, and is highly repeatable and reliable with a standard deviation of +/-3 per thousand. It is stressed that the quantity of deuterated sample required is extremely small as a result of using BSA as supporter. The method may be applied in many fields, and has the strengths of simplicity, relative cheapness, and robustness.

Biopolímeros/análise , Biopolímeros/química , Deutério/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microquímica/métodos , Soroalbumina Bovina/análise , Soroalbumina Bovina/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade