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1.
Int J Infect Dis ; 97: 47-53, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531432

RESUMO

PURPOSE: To explore the molecular genetic mechanisms underlying different responsiveness to Enterovirus 71 (EV71) vaccine. METHODS: We recruited 10,245 healthy children into a phase 3 clinical trial to evaluate the efficacy of EV71 vaccine in 2012. Fifty subjects from the trial were divided into the potent immune response group (20 subjects) and the ineffective immune response group (30 subjects). Whole-exome sequencing was performed for these 50 samples and we conducted bioinformatics analyses based on online public database. RESULTS: A total of 222,180 germline variants were detected across 50 subjects. Single nucleotide variant (SNV)-based screening of the subjects with potent or ineffective immune response allowed the identification of a potentially detrimental heterozygous missense variant (c.3784C>T) in EEA1. We also retained TRIM59 and ABCA7 genes that contain different loss of function (LoF) variants shared in two cases and involved in the immune response process. Then, we conducted high-resolution typing of 9 classical HLA genes, HLA-DRB1*03:01, HLA-DQA1*05:01 and HLA-DQB1*02:01 alleles were frequently (recurrence ≥5) observed only in ineffective immune responders. CONCLUSIONS: Our study is a meaningful attempt on the comparison of genomic profiles between potent and ineffective immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified.

2.
J Infect Dis ; 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32563194

RESUMO

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe and convalescent SARS-CoV-2 infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were signicfiantly higher in SARS-CoV-2-infected male patients than female cases. The serum levels of MCP-1, G-CSF, and VEGF were weekly and positively correlated with the viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluate the severity of COVID-19 and optimize the therapeutic strategies.

3.
Virus Res ; 285: 198005, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32408156

RESUMO

Accumulating evidence shows that microbial co-infection increases the risk of disease severity in humans. There have been few studies about SARS-CoV-2 co-infection with other pathogens. In this retrospective study, 257 laboratory-confirmed COVID-19 patients in Jiangsu Province were enrolled from January 22 to February 2, 2020. They were re-confirmed by real-time RT-PCR and tested for 39 respiratory pathogens. In total, 24 respiratory pathogens were found among the patients, and 242 (94.2 %) patients were co-infected with one or more pathogens. Bacterial co-infections were dominant in all COVID-19 patients, Streptococcus pneumoniae was the most common, followed by Klebsiella pneumoniae and Haemophilus influenzae. The highest and lowest rates of co-infections were found in patients aged 15-44 and below 15, respectively. Most co-infections occurred within 1-4 days of onset of COVID-19 disease. In addition, the proportion of viral co-infections, fungal co-infections and bacterial-fungal co-infections were the highest severe COVID-19 cases. These results will provide a helpful reference for diagnosis and clinical treatment of COVID-19 patients.

4.
Virology ; 546: 122-126, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32452410

RESUMO

Since SARS-CoV-2 spreads rapidly around the world, data have been needed on the natural fluctuation of viral load and clinical indicators associated with it. We measured and compared viral loads of SARS-CoV-2 from pharyngeal swab, IgM anti-SARS-CoV-2, CRP and SAA from serum of 114 COVID-19 patients on admission. Positive rates of IgM anti-SARS-CoV-2, CRP and SAA were 80.7%, 36% and 75.4% respectively. Among IgM-positive patients, viral loads showed different trends among cases with different severity, While viral loads of IgM-negative patients tended to increase along with the time after onset. As the worsening of severity, the positive rates of CRP and SAA also showed trends of increase. Different CRP/SAA type showed associations with viral loads in patients in different severity and different time after onset. Combination of the IgM and CRP/SAA with time after onset and severity may give suggestions on the viral load and condition judgment of COVID-19 patients.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Imunoglobulina M/sangue , Pneumonia Viral/diagnóstico , Carga Viral , Adolescente , Adulto , Idoso , Betacoronavirus , Biomarcadores/sangue , Proteína C-Reativa/análise , Criança , Infecções por Coronavirus/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Faringe/virologia , Pneumonia Viral/sangue , Proteína Amiloide A Sérica/análise , Adulto Jovem
5.
Lancet ; 395(10240): 1845-1854, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32450106

RESUMO

BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/administração & dosagem , Adenoviridae , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus , China , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/uso terapêutico , Vacinas Virais/efeitos adversos , Vacinas Virais/uso terapêutico , Adulto Jovem
6.
Environ Microbiol ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32319181

RESUMO

Vibrio cholerae can enter a viable but non-culturable (VBNC) state when it encounters unfavourable environments; VBNC cells serve as important reservoirs and still pose threats to public health. The genetic regulation of V. cholerae entering its VBNC state is not well understood. Here, we show a confrontation strategy adapted by V. cholerae O1 in which it utilizes a quorum sensing (QS) system to prevent transition into a VBNC state under low nutrition and temperature conditions. The upregulation of hapR resulted in a prolonged culturable state of V. cholerae in artificial sea water at 4°C, whereas the mutation of hapR led to fast entry into the VBNC state. We also observed that different V. cholerae O1 natural isolates with distinct QS functions present a variety of abilities to maintain culturability during the transition to a VBNC state. The strain groups with higher or constitutive expression of QS genes exhibit a greater tendency to maintain the culturable state during VBNC induction than those lacking QS functional groups. In summary, HapR-mediated QS regulation is associated with the transition to the VBNC state in V. cholerae. HapR expression causes V. cholerae to resist VBNC induction and become dominant over competitors in changing environments.

7.
Hum Vaccin Immunother ; : 1-8, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32347785

RESUMO

Mismatch between circulating influenza B viruses and vaccine strains occurs frequently. In a randomized, double-blind, controlled phase III clinical study, healthy children aged 6-35 months were randomized into three groups at a ratio of 2:1:1, received two doses of quadrivalent influenza vaccines (QIVs) or licensed trivalent influenza vaccines (TIVs). The primary objective was to evaluate the non-inferiority immunogenicity of QIV compared with the two TIVs, containing B/Victoria or B/Yamagata strain. Safety information was collected for 28 days after each vaccination. Serious adverse events (SAEs) were monitored for 6 months after the second vaccination. A total of 2146 subjects (QIV: 1069, TIV-Vic: 540, TIV-Yam: 537) were enrolled in this study. QIV was found non-inferior to TIVs for shared strains (A/H1N1 and A/H3N2) and corresponding BY strain based on hemagglutination inhibition (HI) antibodies 28 days after the second dose of vaccination. The resulted geometric mean titer (GMT) ratios (QIV/TIV) were 0.98 (0.89, 1.07) for H1N1, 0.95 (0.85, 1.05) for H3N2 and 0.89 (0.81, 0.98) for BY. And the seroconversion rate differences (QIV-TIV) were -0.46% (-3.24%, 2.31%) for H1N1, -1.95% (-5.54%, 1.65%) for H3N2 and -3.58% (-8.11%, 0.95%) for BY. The BV strain in QIV did not reach the non-inferiority criteria, with GMT of 1:52.25 (vs. 1:61.02 of TIV-Vic) and seroconversion rate of 59.49% (vs. 66.85% of TIV-Vic). No increased safety concerns occurred in QIV group. Candidate QIV can provide good protection for children aged 6 to 35 months, and its immunogenicity and safety were proved.Clinical Trials Registration: ClinicalTrials.gov number: NCT03859141.

8.
Hum Vaccin Immunother ; : 1-7, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209003

RESUMO

Enterovirus 71 (EV71) is the dominant pathogen in severe and fatal hand-foot-mouth disease (HFMD) cases. Since 2015, three inactivated EV71 vaccines have been approved in China. The vaccination coverage of the EV71 vaccine has been relatively low, especially in rural areas. A cross-sectional survey from July 19 to August 22, 2018, was conducted in three rural counties of northern Jiangsu Province among parents of children aged 6-60 months. We adopted a pretested validated questionnaire to assess knowledge, awareness, and attitude of HFMD and EV71 vaccines among respondents and used univariate and multivariate binary logistic analyses to explore potential factors associated with the acceptance of EV71 vaccines. Of the 1,112 parents who participated, 87.8% were willing to vaccinate their children with EV71 vaccines. Parents over 40 y old were less likely to have their children vaccinated [adjusted odds ratio (aOR) = 2.12, 95% confidence interval (CI): 1.13-3.97]. Parents who lived in Ganyu (aOR = 0.50, 95% CI: 0.31-0.79) or Xinyi county (aOR = 0.33, 95% CI: 0.20-0.53), had a university or higher degree (aOR = 0.26, 95% CI: 0.11-0.64), had good knowledge of EV71 vaccines (aOR = 0.81, 95% CI: 0.67-0.98), perceived their children's disease susceptibility, and worried about the severity of HFMD had a higher willingness to vaccinate their children. Most parents were willing to vaccinate their children against EV71-related HFMD. Parental age, location, education level, knowledge of EV71 vaccines, concern about susceptibility, and severity of HFMD were all factors that influenced willingness to vaccinate.

9.
Hum Vaccin Immunother ; : 1-8, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186950

RESUMO

Background: Compared with trivalent influenza vaccines, quadrivalent influenza vaccines are expected to provide wider protection against influenza B virus infections. We developed a novel quadrivalent subunit influenza vaccine which was distinct from the influenza vaccines available on the market in production process. In this research, we evaluated the safety and immunogenicity of the quadrivalent subunit influenza vaccine in animal models.Methods: In toxicity assessment, 40 SD rats were randomly assigned to be intramuscularly injected with 1.0 ml of the tested vaccine (33 µg/ml) or 0.9% sodium chloride solution. In irritation assessment, eight rabbits were randomly assigned to receive 0.5 ml of tested vaccine or phosphate buffer solution intramuscularly. Thirty-two guinea pigs were randomly assigned to be intramuscularly injected with high-dose tested vaccine (0.5 ml), low-dose tested vaccine (0.05 ml), ovalbumin, or 0.9% sodium chloride solution, respectively, for sensitization assessment. In immunogenicity assessment, 50 BALB/c mice were equally randomized to receive one dose of tested vaccine, two doses of tested vaccine with an interval of 14 days, 0.5 ml of trivalent subunit influenza vaccine, 0.5 ml of monovalent subunit influenza vaccine, or 0.5 ml of phosphate buffer solution. Orbital blood was collected before and 28 and 42 days after administration of the injections for detecting influenza antibody titers.Results: No abnormal toxicity and irritation in rats and rabbits showed in the gross autopsy and histopathological examinations. The results of sensitization in guinea pigs indicated that no obvious allergic symptoms observed in the high-dose and low-dose vaccine groups within 30 min after twice provocations, and the result of sensitization evaluation was negative. Vaccine induced significant immune responses in mice with 100% seroconversion rates at 28 and 42 days after the first dose. The geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies at day 28 in one-dose quadri-vaccine and two-dose quadri-vaccine groups were comparable to those in the tri-vaccine or mono-vaccine groups for shared influenza strains. However, the GMTs of HI antibodies against H1N1 (P = 0.025) and BV (P = 0.049) at day 42 in one-dose quadri-vaccine group were significantly lower than those in the tri-vaccine or mono-vaccine groups. The GMTs of HI antibodies against H1N1, H3N1, BY, and BV at day 28 and day 42 were comparable between one-dose quadri-vaccine and two-dose quadri-vaccine groups.Conclusions: The quadrivalent subunit influenza vaccine was safe and immunogenic in animal models. One dose of the vaccine could elicit a satisfactory antibody response in mice.

10.
BMC Infect Dis ; 20(1): 103, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019494

RESUMO

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an endemic communicable disease in China, accounting for 90% of total reported cases worldwide. In this study, the authors want to investigate the risk factors for HFRS in recent years to provide the prevention and control advices. METHODS: A community-based, 1:2 matched case-control study was carried out to investigate the risk factors for HFRS. Cases were defined as laboratory-confirmed cases that tested positive for hantavirus-specific IgM antibodies. Two neighbourhood controls of each case were selected by sex, age and occupation. Standardized questionnaires were used to collect information and identify the risk factors for HFRS. RESULTS: Eighty-six matched pairs were investigated in the study. The median age of the cases was 55.0 years, 72.09% were male, and 73.26% were farmers. In the multivariate logistic regression analysis, cleaning spare room at home (OR = 3.310, 95%CI 1.335-8.210) was found to be risk factor for infection; storing food and crops properly (OR = 0.279 95%CI 0.097-0.804) provided protection from infection. CONCLUSION: Storing food and crops properly seemed to be protective factor, which was important for HFRS prevention and control. More attention should be paid to promote comprehensive health education and behaviour change among high-risk populations in the HFRS endemic area.


Assuntos
Febre Hemorrágica com Síndrome Renal/etiologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , China , Fazendeiros , Feminino , Vírus Hantaan/imunologia , Vírus Hantaan/patogenicidade , Febre Hemorrágica com Síndrome Renal/transmissão , Humanos , Imunoglobulina M/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Controle de Roedores
12.
Sci China Life Sci ; 63(4): 582-591, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31231780

RESUMO

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

13.
Hum Vaccin Immunother ; 16(3): 513-522, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-31545124

RESUMO

Vaccination has been one of the major revolutions in the history of human health. Vaccination programs have targeted entire populations such as infants or elderly subjects as a matter of being efficient with time and resources. These general populations are heterogeneous in terms of factors such as ethnicity, health status, and socio-economics. Thus, there have been variations in the safety and effectiveness profiles of certain vaccinations according to current population-wide strategies. As the concept of precision medicine has been raised in recent years, many researchers have suggested that vaccines could be administered more precisely in terms of particular target populations, vaccine formulations, regimens, and dosage levels. This review addresses the concept and framework of precision immunization, summarizes recent and representative clinical trials of among specific populations, mentions important factors to be addressed in customizing vaccinations, and provides suggestions on the establishment of precision immunization with the goal of maximizing the effectiveness of vaccines in general.

14.
J Natl Cancer Inst ; 112(2): 145-153, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31086947

RESUMO

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

15.
Pediatr Infect Dis J ; 38(11): 1150-1158, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31626050

RESUMO

BACKGROUND: 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in China based on immunologic noninferiority to 7-valent PCV (PCV7). As part of the noninferiority study, immunogenicity and safety of PCV13 administered as a 3- or 2-dose infant series followed by a toddler dose were examined in healthy Chinese infants. METHODS: Infants (42- to 77-days-old) were randomized to a 3-dose PCV13 or PCV7 infant series administered double-blind at 3, 4 and 5 months or PCV13 administered open-label at 2, 4 and 6 months and a 2-dose open-label series at 3 and 5 months; all subjects received a toddler dose (12 months). Serotype-specific immunoglobulin G (IgG) concentrations were measured 1 month after the infant series and before and after the toddler dose. Opsonophagocytic activity (OPA) was measured in a subset of subjects at each time point. Safety was evaluated. RESULTS: One month after the infant series, serotype-specific immune responses (IgG ≥ 0.35 µg/mL) were similar for the 2- versus 3-dose schedules, except for serotype 6B, which was significantly lower in the 2-dose group [70.1% in the PCV13 (3, 5 + 12 mo) group vs. 93.2% in the PCV13 (3, 4, 5 + 12 mo) group and 94.7% in the PCV13 (2, 4, 6 + 12 mo) group]. IgG geometric mean concentrations and OPA geometric mean titers trended numerically higher with 3- versus 2-dose schedules. No significant differences in immunogenicity were observed between the 3- versus 2-dose schedules after the toddler dose. PCV13 was well-tolerated across all schedules. CONCLUSIONS: PCV13 administered as a 3- or 2-dose infant series followed by a toddler dose was immunogenic and well tolerated in healthy Chinese infants and likely protective against PCV13 serotypes; immune responses with a 2-dose schedule were lower for some serotypes.

16.
Open Forum Infect Dis ; 6(10): ofz380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31660344

RESUMO

Background: A new Sabin strain inactivated poliovirus vaccine (sIPV) proved to be immunogenic and safe in all IPV primary immunization in the previous study, with the corresponding profiles in sequential immunizations unclear. Methods: Two clinical trials on the "IPV + 2 bivalent oral polio vaccine (2bOPV)" (Trial A) and "2IPV + bOPV" (Trial B) vaccination were conducted. Both clinical trials were randomized, controlled, double-blinded, noninferiority trials, and wild-strain IPV (wIPV) was adopted as the control vaccine. In each clinical trial, 240 healthy infants were enrolled and randomly assigned to receive sequential vaccinations containing sIPV or wIPV. Immunogenicity and safety were assessed using per-protocol and safety populations, respectively. Results: For Trial A, the seroconversion rates in the experimental and control groups were 100% and 99.1%, respectively, against type 1; both 100.0% against type 3. For Trial B, the seroconversion rates in experimental and control groups were 99.2% and 100.0%, respectively, against type 1; both 100% against type 3. No serious adverse events related to vaccines were reported. Conclusions: The new sIPV demonstrated an immunogenicity noninferior to that of the wIPV and a good safety profile in sequential vaccination with bOPV. Clinical trial numbers: NCT:03822754; NCT:03822767.

17.
Lancet Public Health ; 4(9): e436-e437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31493834
18.
Virology ; 536: 58-67, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400550

RESUMO

Human infection with H7N9 virus has provoked global public health concern due to the substantial morbidity and mortality. Neuraminidase inhibitors (NAIs) are used as first-line drugs to treat the infection. However, virus quasispecies can evolve rapidly under drug pressure, which may alter various biological characteristics of virus. Using an in vitro evolution platform and next-generation sequencing, we found the presence of peramivir led to changes to the dominant populations of the virus. Two important amino acid substitutions were identified in NA, I222T and H274Y, which caused reduced susceptibilities to oseltamivir or both oseltamivir and peramivir as confirmed by enzyme- and cell-based assays. The NA-H274Y variant showed decreased replicative fitness at the early stage of infection accompanied with impaired NA function. The quasispecies evolution of H7N9 virus and the potential emergence of these two variants should be closely monitored, which may guide the adjustment of antiviral strategies.


Assuntos
Antivirais/farmacologia , Ciclopentanos/farmacologia , Farmacorresistência Viral/genética , Guanidinas/farmacologia , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Neuraminidase/genética , Proteínas Virais/genética , Substituição de Aminoácidos , Animais , Cães , Evolução Molecular , Expressão Gênica , Humanos , Subtipo H7N9 do Vírus da Influenza A/enzimologia , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/crescimento & desenvolvimento , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Neuraminidase/metabolismo , Oseltamivir/farmacologia , Carga Viral/efeitos dos fármacos , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacos
19.
Hum Vaccin Immunother ; 15(12): 2952-2959, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31348731

RESUMO

Background: This exploratory study aimed to assess the immunogenicity and safety of 1 and 2 doses of meningococcal serogroups A and C tetanus toxoid-conjugate vaccine (MenAC-TT) in toddles.Methods: Healthy participants aged 12-23 months were randomized into two groups to receive 1 or 2 doses of the tested vaccine. The interval was 28 days between two doses. Blood samples were collected at day 0 before the immunization and day 28 post-each dose. Safety observation was conducted during 28 days after each vaccination. Serious adverse event (SAE) was conducted throughout 6 month observation period.Results: Overall 301 toddles were vaccinated. Twenty-eight days post full-course vaccination, ≥97.20% toddles had titers ≥1:8 and ≥81.48% had titers ≥1:128 for MenA and MenC in the two schedules groups. There were no significant differences between the two schedule groups for each titer thresholds and serogroups. Up to month 12 post the first dose, titers ≥1:8 and 1:128 were declined to 71.32-80.83% and 26.67-57.85% for each meningococcal serogroups. Most adverse reactions (ARs) were mild or moderate, and the incidence of grade 3 ARs was below 3.33%. The incidence of redness was significantly higher in the two doses group than that in the one dose group, in terms of grade 1 and grade 2 were higher. No SAEs were considered causally related to vaccination.Conclusion: The MenAC-TT showed similarly safety and immunogenicity profile in toddles with two schedules. It will be more important to provide the data for formulating appropriate immunization strategies in different age groups in China.


Assuntos
Anticorpos Antibacterianos/sangue , Esquemas de Imunização , Imunogenicidade da Vacina , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Toxoide Tetânico/imunologia , China , Feminino , Humanos , Lactente , Masculino , Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Neisseria meningitidis , Sorogrupo , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
20.
Cancer Med ; 8(14): 6195-6211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31305011

RESUMO

BACKGROUND: Cervical cancer is a major public health concern in China. We report the end-of-study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04-human papillomavirus (HPV)-16/18 vaccine in Chinese women aged 18-25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported. METHODS: Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of AS04-HPV-16/18 vaccine or Al(OH)3 (control) at Months 0-1-6. Vaccine efficacy against HPV-16/18 infection and cervical intraepithelial neoplasia (CIN), cross-protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according-to-protocol efficacy (ATP-E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC-E; vaccine N = 2987; control N = 2985) and TVC-naïve (vaccine N = 1660; control N = 1587). RESULTS: In initially HPV-16/18 seronegative/DNA-negative women, vaccine efficacy against HPV-16/18-associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP-E, 88.7% (95% CI: 18.5, 99.7) in the TVC-E, and 100% (95% CI: 17.9, 100) in the TVC-naïve. Cross-protective efficacy against incident infection with HPV-31, HPV-33 and HPV-45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP-E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and anti-HPV-18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group. CONCLUSIONS: This is the first large-scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV-16/18-associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China. TRIAL REGISTRATION: NCT00779766.

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