Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is litt...Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.展开更多
AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were s...AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.展开更多
Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America ...Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.展开更多
AIM： To evaluate a low cost Indian recombinant hepatitis B vaccine GeneVac-B for its immunogenicity and safety in comparison to Engerix B and Shanvac B vaccine in high risk newborn infants born to （hepatitis B surfa...AIM： To evaluate a low cost Indian recombinant hepatitis B vaccine GeneVac-B for its immunogenicity and safety in comparison to Engerix B and Shanvac B vaccine in high risk newborn infants born to （hepatitis B surface antigen） HBsAg positive mothers.METHODS： A total of 158 infants were enrolled in the study. Fifty eight infants were enrolled in the GeneVac-B group while 50 each were included for Engerix B and Shanvac B groups. A three-dose regimen of vaccination; at birth （within 24 h of birth）, 1st mo and 6 too. were adopted with 10 μg dosage administered uniformly in all the three groups. Clinical and immunological parameters were assessed for safety and immunogenicity of the vaccines, in all the enrolled infants.RESULTS： Successful follow up until seven months of age was achieved in 83% （48/58） for GeneVac-B, 76% （38/50） and 64% （32/50） for Engerix B and Shanvac B groups respectively. 100% seroconversion and seroprotection was achieved in all the three groups of infants. The geometric mean titers of anti-HBs one month after the completion of three dose of vaccination were 90.5, 80.9 and 72.5 mTU/mL in GeneVac-B, Engerix B and Shanvac B vaccine group respectively. Furthermore the level of anti-HBs increases with age of babies who were born to HBsAg positive mothers. The GMT values of anti-HBs were 226.7, 193.9 and 173.6 mIU/mL respectively in GeneVac-B, Engerix B and Shanvac B groups one year after the completion of the three doses of vaccine. No systemic reactions were reported in infants during the entire vaccination process of GeneVac-B and the other two vaccines. Clinical safety parameters remained within the normal limits throughout the study period.CONCLUSION： The study concludes that there is no significant difference between the three recombinant hepatitis B vaccines. Administration of these vaccines within 24 h of birth to babies, born to HBsAg positive mothers will reduce the incidence of HBV infection.展开更多
[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bact...[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bacteriostasis against known serotype E. coli O2 was conducted using microcheckerboard method.[Result] The MIC of rhizoma coptidis, folium isatidis and flos poprli were 1/8 extracting liquid, 1/8 extracting liquid and 1/2 extracting liquid, respectively. When combined with folium isatidis or flos poprli, the MIC of rhizoma coptidis was 1/8 extracting liq-uid or 1/16 extracting liquid compared with single use. When combined with rhizoma coptidis, the MIC of folium isatidis and flos poprli were 1/8 extracting liquid and 1/16 extracting liquid.[Conclusion] When rhizoma coptidis was combined with folium isatidis or flos poprli, the FIC values were 2 and 0.625, performing independent action and additive effect, respectively.展开更多
Neisseria meningitidis is a gram negative diplococcal bacterium. Worldwide, N. meningitidis is the leading cause of bacterial meningitis and sepsis, with five serogroups (A, B, C, Y, and W-135) responsible for the maj...Neisseria meningitidis is a gram negative diplococcal bacterium. Worldwide, N. meningitidis is the leading cause of bacterial meningitis and sepsis, with five serogroups (A, B, C, Y, and W-135) responsible for the majority of the disease. Multivalent (A, C, Y, and W-135) polysaccharide and conjugate vaccines have been licensed in the United States and elsewhere and are widely available. We have developed a multi-plexed electrochemiluminescent assay to quantitate serum antibody responses to meningococcal polysaccharides A, C, Y, and W-135 to allow for rapid evaluation of li- censed and investigational vaccines. A 96-well plate containing a carbon electrode arrayed with polysaccharides A, C, Y, and W-135 on separate spots within each well has been developed for simultaneous detection of polysaccharidespecific antibodies in serum samples from vaccinated individuals. The assay conditions were optimized using the anti-meningococcal serogroup A/C reference serum pool, CDC 1992 (NIBSC 99/706), through evaluation of plate types, coating polysaccharide concentrations, and blocking and serum diluent buffers. Comparison of single and multiplex assays demonstrated the sensitivity, specificity, and speed of the multi-plex format for the quantification of serum antibody responses to N. meningitidis polysaccharides A, C, Y and W-135.展开更多
A high-throughput Serum Bactericidal Assay (SBA) was developed to monitor the functional antibody responses to capsular polysaccharide antigens from multiple serotypes of Neisseria meningitidis. This assay measures th...A high-throughput Serum Bactericidal Assay (SBA) was developed to monitor the functional antibody responses to capsular polysaccharide antigens from multiple serotypes of Neisseria meningitidis. This assay measures the ability of an antibody, aided by complement, to mediate killing of bacteria. Functional assays of this type are increasingly used in the quality control arena as potency release tests. Consequently, there has been an enhanced requirement for reproducibility in the performance of this type of assay. Assay validation is, therefore, important to facilitate understanding of the significance of values obtained, and to enable appropriate and informed use of the assay. This study involved the evaluation of the high-throughput serum bactericidal assay including the effects of different dilution and transfer techniques on assay performance. The results presented here demonstrate the repeatability, and the precision and ruggedness of the assay.展开更多
Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,p...Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.展开更多
Dear Editor,Group B coxsackieviruses(CVBs),belonging to the genus Enterovirus(EV)of the family Picornaviridae,comprise six serotypes and share a typical picornaviral structure(Alhazmi et al.,2023).While most CVB infec...Dear Editor,Group B coxsackieviruses(CVBs),belonging to the genus Enterovirus(EV)of the family Picornaviridae,comprise six serotypes and share a typical picornaviral structure(Alhazmi et al.,2023).While most CVB infections are mild and self-limiting,they can cause severe or fatal illness,especially in children(Tracy and Gauntt,2008).展开更多
Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,altho...Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,although the underlying mechanisms have yet to be determined.We examined the effects of 3ʹ-SL on glycolipid metabolism in mice fed a high-fat diet.Male C57BL/6J mice were divided into 6 groups:2 model control groups(normal and high-fat diets)and 4 intervention groups(Neu5Ac,and low,moderate,and high-dose 3ʹ-SL).After 8 weeks of continuous gavage intervention,mice in the 3ʹ-SL intervention groups had lower body weight and total fat content;reduced fasting blood glucose,triglycerides,low-density lipoproteins and oxidized-low-density lipoproteins;and increased high-density lipoproteins,but no dosage-dependent of 3ʹ-SL intervention was found,moderate-dose 3ʹ-SL intervention as optimal for further exploration.3ʹ-SL intervention could increase respiratory exchange ratio,energy expenditure,and amount of exercise performed.3ʹ-SL increased the colonic abundances of Akkermansia,Lactobacillus,and Bacteroides,and reduced those of Erysipelatoclostridium,Faecalibaculum,and Aldercreutzia.Changes were also observed in colonic metabolites,and liver gene transcript and metabolites,which were mainly enriched in bile secretion,taurine and hypotaurine metabolism,and insulin resistance.Additionally,3ʹ-SL was observed to regulate genes associated with physiological rhythms,including Clock,Per2,Cry1,and Bhihe41.Collectively,our findings indicate that 3ʹ-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets.Compared with Neu5Ac,3ʹ-SL intervention can more effectively ameliorate intestinal flora disorders,enhance bile acid circulation,increase tissue energy expenditure,and reduce lipid synthesis,thereby promoting lipid-lowering effects mediated via the gut-liver axis,and can also enhance energy metabolism and alleviate disorders of glucolipid metabolism by altering physiological rhythms in high fat-diet mice.展开更多
Background:Human papillomavirus(HPV)infection is a major risk factor of cervical cancer.This study assessed the prevalence and distribution of HPV genotypes in women with cervical or vaginal lesions in Jiangsu Provinc...Background:Human papillomavirus(HPV)infection is a major risk factor of cervical cancer.This study assessed the prevalence and distribution of HPV genotypes in women with cervical or vaginal lesions in Jiangsu Province,China.Methods:A total of 2120 healthy women aged 18–45 years were screened between 2012 and 2013 and 6171 healthy women aged18–45 years were screened between 2020 and 2021 in Jiangsu Province.Cervical specimens collected from each woman were first tested using the HPV DNA enzyme immunoassay method,and positive samples were further tested using the reverse hybridization line probe assay.Differences in HPV prevalence and genotype distribution were compared between women with cervical and vaginal lesions identified during 2 rounds of cross-sectional screening.To account for differences in age composition between the 2 studies,the standardized prevalence of HPV positivity was calculated using the sum of the total number of women diagnosed with cervical or vaginal lesions during both periods as the standard group.Results:Overall,40 women(1.89%)were diagnosed with cervical or vaginal lesions through biopsy during 2012–2013,and 110(1.78%)were diagnosed during 2020–2021.Among women with lesions,the standardized HPV positivity rates were 98.41%in 2012–2013 and99.24%in 2020–2021.Most cases were caused by high-risk HPV,which accounted for 87.18%of the total infections during 2012–2013and 89.91%of those in 2020–2021,with standardized positivity rates of 86.44%and 88.75%,respectively.The standardized positivity rates for single infections were 62.35%in 2012–2013 and 74.95%in 2020–2021.The top 5 high-risk HPV genotypes were HPV type 16(HPV16;29.01%),52(20.63%),18(14.28%),58(13.71%),and 33(12.12%)in 2012–2013,and HPV16(36.95%),58(22.18%),52(13.25%),31(7.63%),and 51(6.81%)in 2020–2021.The standardized positivity rate for HPV18 decreased from 14.28%in2012–2013 to 1.15%in 2020–2021.Among women with cervical or vaginal lesions,the highest proportion was observed in the 36-to 45-year group during 2012–2013,reaching 52.50%,and in the 26-to 35-year group during 2020–2021,peaking at 59.10%.Conclusions:In Jiangsu Province,no significant changes in HPV prevalence among women with cervical or vaginal lesions were observed during 2012–2013 and 2020–2021;however,the distribution of HPV genotypes had changed.展开更多
Since the outbreak of COVID-19 in late 2019,the cumulative number of confirmed cases worldwide has surpassed 778 million,and the number of deaths has exceeded 7 million,posing a significant threat to human life and he...Since the outbreak of COVID-19 in late 2019,the cumulative number of confirmed cases worldwide has surpassed 778 million,and the number of deaths has exceeded 7 million,posing a significant threat to human life and health while inflicting enormous losses on the global economy.At the stage where sequential immunization is recommended,there is a pressing demand for mRNA vaccines that can be rapidly adapted to new sequences,are easy to industrialize,and exhibit high safety and effectiveness.We developed a lipid nanoparticle(LNP)system,designated as WNP,which facilitates essentially in situ expression at the injection site and results in lower levels of pro-inflammatory factors in the liver,thus enhancing its safety compared to liver-targeted alternatives.Furthermore,in light of the swiftly mutating characteristic of SARS-CoV-2,a study has used cross-lineage chimeras and mutation patch strategies to design an antigen that is highly immunogenic and can stimulate the production of a broad range of effective antibodies.Therefore,we used the same antigenic configuration of RBD including five key mutation sites(K417T,L452R,T478K,E484K,and N501Y)to achieve optimal broad-spectrum efficacy.Our results indicate that WNP can elicit a humoral immunity response that is as robust as that of SM-102,a stronger cellular immune response,and provide a certain protective effect.On top of that,WNP can be applied to the development of vaccines targeting other pathogens and will contribute to a quicker response to the spillovers of unknown mammalian viruses.展开更多
We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mu...We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript(LAT) gene. Observations of the resulting mutants with modified UL7 and UL41(M2) or UL7, UL41 and LAT(M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.展开更多
基金supported by the National Key R&D Program of China(2020YFC0849700)the Program of Chinese Academy of Medicine Sciencethe Major Science and Technology Special Projects of Yunnan Province。
文摘Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.
基金Serum Institute of India, Pune, India and Indian Council for Medical Research (ICMR) New Delhi, India
文摘AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.
基金supported in part by the National Key Program Project Grant from MOST #2016YFC1201000
文摘Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.
文摘AIM： To evaluate a low cost Indian recombinant hepatitis B vaccine GeneVac-B for its immunogenicity and safety in comparison to Engerix B and Shanvac B vaccine in high risk newborn infants born to （hepatitis B surface antigen） HBsAg positive mothers.METHODS： A total of 158 infants were enrolled in the study. Fifty eight infants were enrolled in the GeneVac-B group while 50 each were included for Engerix B and Shanvac B groups. A three-dose regimen of vaccination; at birth （within 24 h of birth）, 1st mo and 6 too. were adopted with 10 μg dosage administered uniformly in all the three groups. Clinical and immunological parameters were assessed for safety and immunogenicity of the vaccines, in all the enrolled infants.RESULTS： Successful follow up until seven months of age was achieved in 83% （48/58） for GeneVac-B, 76% （38/50） and 64% （32/50） for Engerix B and Shanvac B groups respectively. 100% seroconversion and seroprotection was achieved in all the three groups of infants. The geometric mean titers of anti-HBs one month after the completion of three dose of vaccination were 90.5, 80.9 and 72.5 mTU/mL in GeneVac-B, Engerix B and Shanvac B vaccine group respectively. Furthermore the level of anti-HBs increases with age of babies who were born to HBsAg positive mothers. The GMT values of anti-HBs were 226.7, 193.9 and 173.6 mIU/mL respectively in GeneVac-B, Engerix B and Shanvac B groups one year after the completion of the three doses of vaccine. No systemic reactions were reported in infants during the entire vaccination process of GeneVac-B and the other two vaccines. Clinical safety parameters remained within the normal limits throughout the study period.CONCLUSION： The study concludes that there is no significant difference between the three recombinant hepatitis B vaccines. Administration of these vaccines within 24 h of birth to babies, born to HBsAg positive mothers will reduce the incidence of HBV infection.
基金Supported by Natural Science Foundation of Shandong Province(ZR2014CQ012)
文摘[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bacteriostasis against known serotype E. coli O2 was conducted using microcheckerboard method.[Result] The MIC of rhizoma coptidis, folium isatidis and flos poprli were 1/8 extracting liquid, 1/8 extracting liquid and 1/2 extracting liquid, respectively. When combined with folium isatidis or flos poprli, the MIC of rhizoma coptidis was 1/8 extracting liq-uid or 1/16 extracting liquid compared with single use. When combined with rhizoma coptidis, the MIC of folium isatidis and flos poprli were 1/8 extracting liquid and 1/16 extracting liquid.[Conclusion] When rhizoma coptidis was combined with folium isatidis or flos poprli, the FIC values were 2 and 0.625, performing independent action and additive effect, respectively.
文摘Neisseria meningitidis is a gram negative diplococcal bacterium. Worldwide, N. meningitidis is the leading cause of bacterial meningitis and sepsis, with five serogroups (A, B, C, Y, and W-135) responsible for the majority of the disease. Multivalent (A, C, Y, and W-135) polysaccharide and conjugate vaccines have been licensed in the United States and elsewhere and are widely available. We have developed a multi-plexed electrochemiluminescent assay to quantitate serum antibody responses to meningococcal polysaccharides A, C, Y, and W-135 to allow for rapid evaluation of li- censed and investigational vaccines. A 96-well plate containing a carbon electrode arrayed with polysaccharides A, C, Y, and W-135 on separate spots within each well has been developed for simultaneous detection of polysaccharidespecific antibodies in serum samples from vaccinated individuals. The assay conditions were optimized using the anti-meningococcal serogroup A/C reference serum pool, CDC 1992 (NIBSC 99/706), through evaluation of plate types, coating polysaccharide concentrations, and blocking and serum diluent buffers. Comparison of single and multiplex assays demonstrated the sensitivity, specificity, and speed of the multi-plex format for the quantification of serum antibody responses to N. meningitidis polysaccharides A, C, Y and W-135.
文摘A high-throughput Serum Bactericidal Assay (SBA) was developed to monitor the functional antibody responses to capsular polysaccharide antigens from multiple serotypes of Neisseria meningitidis. This assay measures the ability of an antibody, aided by complement, to mediate killing of bacteria. Functional assays of this type are increasingly used in the quality control arena as potency release tests. Consequently, there has been an enhanced requirement for reproducibility in the performance of this type of assay. Assay validation is, therefore, important to facilitate understanding of the significance of values obtained, and to enable appropriate and informed use of the assay. This study involved the evaluation of the high-throughput serum bactericidal assay including the effects of different dilution and transfer techniques on assay performance. The results presented here demonstrate the repeatability, and the precision and ruggedness of the assay.
基金National Resources Center for Non Human PrimatesNational Key R&D Project of China,Grant/Award Number:2021YFF0702804。
文摘Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.
基金supported by grants from the National Natural Science Foundation of China(82172248,82472253,82272310 and 32470996)the Xiamen Science and Technology Program(2022CXY0102)+1 种基金the Fundamental Research Funds for the Central Universities(20720250004)the Independent Research Project of the State Key Laboratory of Vaccine for Infectious Diseases(2024SKLVDzy03).
文摘Dear Editor,Group B coxsackieviruses(CVBs),belonging to the genus Enterovirus(EV)of the family Picornaviridae,comprise six serotypes and share a typical picornaviral structure(Alhazmi et al.,2023).While most CVB infections are mild and self-limiting,they can cause severe or fatal illness,especially in children(Tracy and Gauntt,2008).
基金supported by the Incubation Fund of Zhongshan Hospital,Fudan University(Xiamen Branch)(2020ZSXMYS24).
文摘Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,although the underlying mechanisms have yet to be determined.We examined the effects of 3ʹ-SL on glycolipid metabolism in mice fed a high-fat diet.Male C57BL/6J mice were divided into 6 groups:2 model control groups(normal and high-fat diets)and 4 intervention groups(Neu5Ac,and low,moderate,and high-dose 3ʹ-SL).After 8 weeks of continuous gavage intervention,mice in the 3ʹ-SL intervention groups had lower body weight and total fat content;reduced fasting blood glucose,triglycerides,low-density lipoproteins and oxidized-low-density lipoproteins;and increased high-density lipoproteins,but no dosage-dependent of 3ʹ-SL intervention was found,moderate-dose 3ʹ-SL intervention as optimal for further exploration.3ʹ-SL intervention could increase respiratory exchange ratio,energy expenditure,and amount of exercise performed.3ʹ-SL increased the colonic abundances of Akkermansia,Lactobacillus,and Bacteroides,and reduced those of Erysipelatoclostridium,Faecalibaculum,and Aldercreutzia.Changes were also observed in colonic metabolites,and liver gene transcript and metabolites,which were mainly enriched in bile secretion,taurine and hypotaurine metabolism,and insulin resistance.Additionally,3ʹ-SL was observed to regulate genes associated with physiological rhythms,including Clock,Per2,Cry1,and Bhihe41.Collectively,our findings indicate that 3ʹ-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets.Compared with Neu5Ac,3ʹ-SL intervention can more effectively ameliorate intestinal flora disorders,enhance bile acid circulation,increase tissue energy expenditure,and reduce lipid synthesis,thereby promoting lipid-lowering effects mediated via the gut-liver axis,and can also enhance energy metabolism and alleviate disorders of glucolipid metabolism by altering physiological rhythms in high fat-diet mice.
基金supported by Xiamen University,which played a key role in the collection and analysis of the datafunded by National Natural Science Foundation of China(grants 82341031,82173584,and 82222062)+2 种基金Major Research Plan of the National Natural Science Foundation of China(grant 92269205)Science Fund for Distinguished Young Scholars of Jiangsu Province(grant BK20220064)Jiangsu Provincial Key Project of Science and Technology Plan(grants BE2021738 and BE2023601)。
文摘Background:Human papillomavirus(HPV)infection is a major risk factor of cervical cancer.This study assessed the prevalence and distribution of HPV genotypes in women with cervical or vaginal lesions in Jiangsu Province,China.Methods:A total of 2120 healthy women aged 18–45 years were screened between 2012 and 2013 and 6171 healthy women aged18–45 years were screened between 2020 and 2021 in Jiangsu Province.Cervical specimens collected from each woman were first tested using the HPV DNA enzyme immunoassay method,and positive samples were further tested using the reverse hybridization line probe assay.Differences in HPV prevalence and genotype distribution were compared between women with cervical and vaginal lesions identified during 2 rounds of cross-sectional screening.To account for differences in age composition between the 2 studies,the standardized prevalence of HPV positivity was calculated using the sum of the total number of women diagnosed with cervical or vaginal lesions during both periods as the standard group.Results:Overall,40 women(1.89%)were diagnosed with cervical or vaginal lesions through biopsy during 2012–2013,and 110(1.78%)were diagnosed during 2020–2021.Among women with lesions,the standardized HPV positivity rates were 98.41%in 2012–2013 and99.24%in 2020–2021.Most cases were caused by high-risk HPV,which accounted for 87.18%of the total infections during 2012–2013and 89.91%of those in 2020–2021,with standardized positivity rates of 86.44%and 88.75%,respectively.The standardized positivity rates for single infections were 62.35%in 2012–2013 and 74.95%in 2020–2021.The top 5 high-risk HPV genotypes were HPV type 16(HPV16;29.01%),52(20.63%),18(14.28%),58(13.71%),and 33(12.12%)in 2012–2013,and HPV16(36.95%),58(22.18%),52(13.25%),31(7.63%),and 51(6.81%)in 2020–2021.The standardized positivity rate for HPV18 decreased from 14.28%in2012–2013 to 1.15%in 2020–2021.Among women with cervical or vaginal lesions,the highest proportion was observed in the 36-to 45-year group during 2012–2013,reaching 52.50%,and in the 26-to 35-year group during 2020–2021,peaking at 59.10%.Conclusions:In Jiangsu Province,no significant changes in HPV prevalence among women with cervical or vaginal lesions were observed during 2012–2013 and 2020–2021;however,the distribution of HPV genotypes had changed.
基金supported by the National Key R&D Program of China(2021YFF0702000 to Y.Chen,2021YFC2300700 to L.Zhou)the National Natural Science Foundation of China(grants 82341061,82172243 and 82372223 to Y.Chen)+2 种基金the Fundamental Research Funds for the Central Universities(2042022dx0003 to Y.Chen)the Hubei Provincial Natural Science Foundation(2023AFB201 to Z.Zhang,and 2024AFB906 to L.Zhou.)the China Postdoctoral Science Foundation(2023M732705 to Q.Liu).
文摘Since the outbreak of COVID-19 in late 2019,the cumulative number of confirmed cases worldwide has surpassed 778 million,and the number of deaths has exceeded 7 million,posing a significant threat to human life and health while inflicting enormous losses on the global economy.At the stage where sequential immunization is recommended,there is a pressing demand for mRNA vaccines that can be rapidly adapted to new sequences,are easy to industrialize,and exhibit high safety and effectiveness.We developed a lipid nanoparticle(LNP)system,designated as WNP,which facilitates essentially in situ expression at the injection site and results in lower levels of pro-inflammatory factors in the liver,thus enhancing its safety compared to liver-targeted alternatives.Furthermore,in light of the swiftly mutating characteristic of SARS-CoV-2,a study has used cross-lineage chimeras and mutation patch strategies to design an antigen that is highly immunogenic and can stimulate the production of a broad range of effective antibodies.Therefore,we used the same antigenic configuration of RBD including five key mutation sites(K417T,L452R,T478K,E484K,and N501Y)to achieve optimal broad-spectrum efficacy.Our results indicate that WNP can elicit a humoral immunity response that is as robust as that of SM-102,a stronger cellular immune response,and provide a certain protective effect.On top of that,WNP can be applied to the development of vaccines targeting other pathogens and will contribute to a quicker response to the spillovers of unknown mammalian viruses.
基金supported by the National Basic Research Program (2012CB518901)Chinese academy of medical sciences (CAMS) Initiative for Innovative Medicine (2016I2M-1-019)+1 种基金the National Natural Science Foundation of China (31300143, 31100127)the Fundamental Research Funds for the Central Universities (2016ZX310047, 2016ZX350072)
文摘We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript(LAT) gene. Observations of the resulting mutants with modified UL7 and UL41(M2) or UL7, UL41 and LAT(M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.
