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1.
Front Microbiol ; 12: 732426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733250

RESUMO

Salmonella spp. is one of the most common foodborne disease-causing pathogens that can cause severe diseases in very low infectious doses. Rapid and sensitive detecting Salmonella spp. is advantageous to the control of its spread. In this study, a conserved short fragment of the Salmonella invA gene was selected and used to design primers and specific crRNA (CRISPR RNA) for establishing a one-tube and two-step reaction system for Salmonella spp. detection, by combining recombinase polymerase amplification (RPA) with CRISPR-Cas13a (Clustered Regularly Interspaced Short Palindromic Repeats associated protein 13a) cleavage. The established one-tube RPA-Cas13a method can complete the detection within 20 min and the two-step RPA-Cas13a method detection time within 45 min. The designed primers were highly specific to Salmonella spp. and had no cross-reaction with the other nine diarrheal bacteria. The one-tube RPA-Cas13a could detect the Salmonella genome with the limit of 102 copies, which was the same as real-time polymerase chain reaction (PCR), but less sensitive than two-step RPA-Cas13a (100 copies). The detection results of one-tube or two-step RPA-Cas13a and real-time PCR were highly consistent in clinical samples. One-tube RPA-Cas13a developed in this study provides a simple, rapid, and specific detection method for Salmonella spp. While two-step assay was more sensitive and suitable for samples at low abundance.

3.
Natl Sci Rev ; 8(8): nwab053, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34676098

RESUMO

Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

4.
Clin Infect Dis ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551104

RESUMO

BACKGROUND: We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine with homologous prime-boost regimens in healthy participants aged 6 years and above. METHODS: In this randomised, double-blind, placebo-controlled trial, participants received low-dose vaccine, middle-dose vaccine or placebo. Prime-booster regimens were given intramuscularly 56 days apart. ELISA antibodies to the receptor binding domain (RBD) and pseudovirus neutralising antibodies were detected. Adverse events were monitored for 28 days following each vaccination. RESULTS: A total of 430 participants were enrolled in the study, with 30 participants aged 18-55 years (MID cohort), 250 participants aged 56 years and older (OLD cohort), and 150 participants aged 6-17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies which decreased with increasing age, with geometric mean titres (GMTs) of 1037.5 in MIN cohort, 647.2 in MID cohort, and 338.0 in OLD cohort receiving 5×10 10 viral particles on day 28 following boost vaccination. Pseudovirus neutralising antibodies showed a similar pattern, with GMTs of 168.0 in MIN cohort, 76.8 in MID cohort, and 79.7 in OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by two doses in adults, with GMTs of 1091.6 and 96.6 in ELISA antibody and neutralising antibody, respectively. Homologous prime-boost vaccination was safety and tolerable. CONCLUSIONS: Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6-17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine.

5.
Microbiol Spectr ; 9(2): e0059021, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34550000

RESUMO

To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P < 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. IMPORTANCE The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Criança , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Memória Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Chin Med J (Engl) ; 134(17): 2037-2044, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34343152

RESUMO

ABSTRACT: With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the importance of vaccines in epidemic prevention and public health has become even more obvious than ever. However, the emergence of multiple severe acute respiratory syndrome coronavirus 2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines. Here, we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them. In addition, we further discuss future directions for the research and development of the next generation of COVID-19 vaccines. We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines, including the thromboembolism caused by the AstraZeneca and Johnson & Johnson vaccines.


Assuntos
COVID-19 , Vacinas , Vacinas contra COVID-19 , Humanos , SARS-CoV-2
7.
Signal Transduct Target Ther ; 6(1): 271, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267185

RESUMO

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Adolescente , Adulto , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Hum Vaccin Immunother ; 17(9): 3162-3168, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33945439

RESUMO

Background: To evaluate the persistence of antibody for 10 years, and investigate the effect of one or two booster doses with Kanghua human diploid cells rabies vaccine (HDCV) in China.Methods: Participants were re-recruited at year 10 post the primary phase 3 clinical study. Some of them in Kanghua HDCV group who had been boosted one dose at year 8, received one more dose at this boosted study. Participants who never boosted were randomly assigned to boost 1 or 2 doses of Kanghua HDCV. Blood samples were collected at day 0, 1, 3, 7, and 14. Safety was evaluated from day 0-14.Results: At year 10 after primary vaccination, the seroconversion rates of neutralizing antibody were 98.28-100% in Kanghua and Pasteur groups.After booster, the seroconversion rate in each group reached to 100% from day 7 to day 14. GMCs were similar in the groups with the same booster doses, and two doses of booster induced higher levels of antibody. The reported rates of solicited local and systemic adverse reaction were low, and no serious adverse events were found through the boosted study.Conclusion: 5 doses of Kanghua HDCV maintained long-term immunity at least 10 years. One or two doses of booster, rapidly triggered 100% protection against rabies virus.Trial registration: ClinicalTrials.gov: NCT03774628.


Assuntos
Vacinas Antirrábicas , Raiva , Anticorpos Antivirais , Diploide , Humanos , Imunização Secundária , Raiva/prevenção & controle , Vacinação
10.
Clin Infect Dis ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34021314

RESUMO

BACKGROUND: Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of the novel ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults. METHODS: We conducted two randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A Bacillus Calmette Guerin (BCG) model was also established to assess the diagnosis of tuberculosis infection using EC skin test. RESULTS: In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive the EC skin test at 1.0µg/0.1ml or 0.5µg/0.1ml. The area under the curve was 0.95 (95% CI, 0.91-0.97) from the EC skin test at a dose of 1.0µg/0.1ml at 24-72 hours. Compared to the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI 77.8-97.2 versus 86.5, 95% CI 79.5-93.4) and specificity (98.9, 95% CI 96.0-99.9 versus 96.1, 95% CI 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed. CONCLUSIONS: The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0µg/0.1ml, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination.

11.
Vaccine ; 39(26): 3509-3515, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33994238

RESUMO

BACKGROUND: Mumps outbreaks in adolescents who received two doses of measles-mumps-rubella vaccine (MMR) during childhood have been reported worldwide. In China, one dose of MMR administered in children aged among 18-24 months has a limited effect on the mumps epidemic. There are limited prospective studies evaluating the mumps immunity profile of children aged 3-7 years who received one dose of MMR. This study aimed to describe mumps immunity profile over a span of 4-years in kindergarten and primary school children. METHODS: An observational, prospective study on one-dose MMR in children aged 3-7 years who underwent blood sample collection in 2015, 2016, and 2018 was conducted from 2015 to 2018. The seropositivity and geometric mean concentration of mumps IgG antibodies over time were analyzed. RESULTS: A total of 3346 eligible children aged 3-7 years who underwent three rounds of blood sample collection were included. The overall seropositivity (79.6%) in 2015 was significantly higher than those recorded in 2016 (73.1%) and 2018 (71.4%). Approximately 11.6-15.9% of the participants were seropositive for mumps in 2015, and converted to negative in 2016. Meanwhile, 11.1-14.6% of the participants were seropositive for mumps in 2016, and the results converted to negative in 2018. Over 6.1-7.4% of the participants had asymptomatic infection from 2015 to 2016, while 9.0-9.9% of the participants were infected without clinical symptoms from 2016 to 2018. CONCLUSIONS: Kindergarten and primary school children who only received one dose of MMR were at higher risk of developing mumps. Waning immunity, seronegative conversion, and asymptomatic infection coexist in children who received one dose MMR. Determining the optimal age for administering the second dose of MMR in children should be prioritized to improve the control and prevention of mumps in China.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Anticorpos Antivirais , Infecções Assintomáticas/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Humanos , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/epidemiologia , Caxumba/prevenção & controle , Estudos Prospectivos
12.
Nat Med ; 27(6): 1062-1070, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33888900

RESUMO

An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 µg or 30 µg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older adults (aged 65-85 years) to each treatment group (ChiCTR2000034825). BNT162b1 encodes the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) and is one of several messenger RNA-based vaccine candidates under clinical investigation. Local reactions and systemic events were generally dose dependent, transient and mild to moderate. Fever was the only grade 3 adverse event. BNT162b1 induced robust interferon-γ T cell responses to a peptide pool including the RBD in both younger and older Chinese adults, and geometric mean neutralizing titers reached 2.1-fold (for younger participants) and 1.3-fold (for the older participants) that of a panel of COVID-19 convalescent human sera obtained at least 14 d after positive SARS-CoV-2 polymerase chain reaction test. In summary, BNT162b1 has an acceptable safety profile and produces high levels of humoral and T cell responses in an Asian population.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , RNA Mensageiro/genética , RNA Mensageiro/imunologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Adulto Jovem
13.
Signal Transduct Target Ther ; 6(1): 165, 2021 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-33895786

RESUMO

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Simulação por Computador , Reposicionamento de Medicamentos , Modelos Biológicos , SARS-CoV-2/metabolismo , Humanos
14.
Chin Med J (Engl) ; 134(11): 1289-1298, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33928916

RESUMO

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 µg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 µg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-µg vaccine (n = 24), 10-µg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-µg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-µg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-µg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-µg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-µg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Vacinas contra COVID-19 , Método Duplo-Cego , Humanos , Vacinas de Produtos Inativados/efeitos adversos
15.
Expert Rev Vaccines ; 20(4): 437-448, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33709863

RESUMO

BACKGROUND: Rotavirus (RV), which causes RV-associated gastroenteritis (RVGE), has accounted for considerable morbidity. We aimed to assess the effectiveness (VE) of the oral pentavalent RV vaccine (RotaTeq™) in real-world settings in children and infants with gastroenteritis. METHODS: We performed a systematic search for peer-reviewed studies published between 1 January 2006 and 1 May 2020 and a meta-analysis to calculate the VE of RotaTeq™ vaccine. The primary outcome was the pooled three-dose vaccine VE. Stratified analysis of the vaccine VEs was performed according to dosages, study design, population age, socioeconomic status (SES), introduction condition, control group types, outcomes of RV disease, and RV strains. RESULTS: After screening 2359 unique records, 28 studies were included and meta-analyzed. The overall VE estimate was 84% (95% confidence interval [CI], 80-87%). Stratified analyses revealed a nonnegligible impact of factors such as study design and SES. Other factors did not show great impart to VE with no significant differences between groups. CONCLUSIONS: RotaTeq™ is effective against RV infection, especially in high-income countries. Adopting suitable study methods and expansion of RV surveillance in low-income regions is crucial to assess VE in real-life settings and provide feasible vaccine regimens to improve vaccine VE.

16.
Emerg Microbes Infect ; 10(1): 555-564, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33682609

RESUMO

As a high-risk factor of perinatal HBV transmission, the potential role of maternal hepatitis B e antigen (HBeAg) to guide antiviral prophylaxis has not yet been fully reported. This large prospective cohort study enrolled 1177 hepatitis B surface antigen (HBsAg)-positive pregnant women without antiviral treatment and their newborns. HBeAg, HBsAg, and viral load in maternal serum collected before delivery were measured. All the newborns were given standard passive-active immunoprophylaxis within 12 h after birth, and post-vaccination serologic testing was performed at 7 (±7d) months of age. The results revealed that 20 of the 1177 infants (1.70%) were immunoprophylaxis failure, and all their mothers were HBeAg positive. Maternal quantitative HBeAg was positively correlated with viral load (r = 0.83; P < .0001) and quantitative HBsAg (r = 0.68; P < .0001). The area under the receiver operating characteristic curve (AUC) for predicting immunoprophylaxis failure by maternal HBeAg was comparable to that by maternal viral load (0.871 vs 0.893; P = .441) and HBsAg (0.871 vs 0.871; P = .965). The optimal cutoff value of maternal quantitative HBeAg to predict perinatal infection was 2.21 log10 PEI U/mL, and the sensitivity and specificity was 100.0% and 74.5%, respectively. According to maternal viral load >2 × 105 IU/mL, the sensitivity and specificity of maternal qualitative HBeAg to identify the risk of HBV MTCT for pregnant women and determine the necessity for antiviral prophylaxis was 95.5% and 92.6%, respectively. This study showed that maternal HBeAg can be a surrogate marker of HBV DNA for monitoring and evaluating whether antiviral prophylaxis is necessary for preventing perinatal HBV transmission.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/prevenção & controle , Hepatite B/virologia , Complicações Infecciosas na Gravidez/virologia , Adolescente , Adulto , Antivirais/uso terapêutico , Área Sob a Curva , China/epidemiologia , DNA Viral , Feminino , Hepatite B/epidemiologia , Hepatite B/transmissão , Vírus da Hepatite B/genética , Humanos , Imunização Passiva , Imunoterapia Ativa , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Filogenia , Gravidez , Prognóstico , Estudos Prospectivos , Fatores de Risco , Testes Sorológicos , Carga Viral , Adulto Jovem
18.
Hum Vaccin Immunother ; 17(8): 2762-2767, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-33735590

RESUMO

This study consisted of two rounds of cross-sectional observations designed to evaluate the persistence of immune protection induced high antigen content hepatitis B (HB) vaccine at 60 µg/1.0 ml formulations administered at a three-dose schedule (Days 0, 28, and 56) in non-responders to routine HB vaccination. In the original phase 3 study, we enrolled 1091 healthy participants (16-60 years old) seronegative for antibody against HB surface antigen (anti-HBs) after primary vaccination. Participants were randomized (2:2:1) to receive three booster doses of HB vaccine containing 60 µg, 30 µg, or 10 µg of antigen per dose 28 days apart. In the group receiving the 60 µg HB vaccine, 428 participants' serum samples were available at pre-vaccination and 28 days after each vaccine dose and were included in immunogenicity analysis. With two written informed consents, we collected blood samples from 276 (67.2%) participants in 2014 and 239 (58.2%) in 2019, who had completed the full course of revaccination and reached the seropositive (anti-HBs≥10 mIU/ml) standard in the 60 µg vaccine group of the original phase 3 study. The HBV seropositive rate was found to decrease from 96.0% in 28 days after receiving the third dose of 60 µg HB vaccine, to 48.2% in 2014, and to 40.6% in 2019, with anti-HBs GMC of seropositive individuals was 584.0 mIU/ml, 142.4 mIU/ml, and 169.1 mIU/ml, respectively. Analysis of 181 vaccinees who had serologic test results available both in 2014 and in 2019, and results revealed a dynamic trend in anti-HBs titer similar to that for the whole immune persistence cohort. Of paramount importance, the serologic test results found that 24.9% (45/181) participants had higher anti-HBs concentrations in 2019 than in 2014, this could be interpreted as natural boosters, secondary to HBV exposure without infection because protected. In conclusion, protective antibody persists about 11 years after immunization of Chinese non-responders with 3 doses of 60 µg HB vaccine. Booster doses of vaccine do not seem necessary to ensure long-term protection.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Adolescente , Adulto , China , Estudos Transversais , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Humanos , Imunização Secundária , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
20.
Emerg Microbes Infect ; 10(1): 365-375, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33583360

RESUMO

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.


Assuntos
Hepatite E/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Vacinas Sintéticas/imunologia , Vacinas contra Hepatite Viral/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Feminino , Hepatite E/prevenção & controle , Hepatite E/virologia , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Imunidade , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/genética , Vacinação/efeitos adversos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas contra Hepatite Viral/administração & dosagem , Vacinas contra Hepatite Viral/efeitos adversos , Vacinas contra Hepatite Viral/genética , Adulto Jovem
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