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ImportancePeople over 60 developed less protection after two doses of inactivated COVID-19 vaccine than younger people. Heterologous vaccination might provide greater immunity and protection against variants of concern. ObjectiveTo assess the safety and immunogenicity of a heterologous immunization with an adenovirus type 5-vectored vaccine (Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. DesignAn observer-blind, randomized (1:1) trial, conducted from August 26 to November 13, 2021. SettingA single center in Jiangsu Province, China. Participants299 participants aged 60 years and older, of them 199 primed with two doses of CoronaVac in the past 3-6 months and 100 primed with one dose of CoronaVac in the past 1-2 months. InterventionConvidecia or CoronaVac as boosting dose Main Outcomes and MeasuresGeometric mean titers (GMTs) of neutralizing antibodies against wild-type SARS-CoV-2, and Delta and Omicron variants 14 days post boosting, and adverse reactions within 28 days. ResultsIn the three-dose regimen cohort (n=199; mean (SD) age, 66.7 (4.2) years; 74 (37.2%) female), 99 and 100 received a third dose of Convidecia (group A) and CoronaVac (group B), respectively. In the two-dose regimen cohort (n=100; mean (SD) age, 70.5 (6.0) years; 49 (49%) female), 50 and 50 received a second dose of Convidecia (group C) and CoronaVac (group D), respectively. GMTs of neutralizing antibodies against wild-type SARS-CoV-2 at day 14 were 286.4 (95% CI: 244.6, 335.2) in group A and 48.2 (95% CI: 39.5, 58.7) in group B, with GMT ratio of 6.2 (95% CI: 4.7, 8.1), and 70.9 (95% CI: 49.5, 101.7) in group C and 9.3 (95% CI: 6.2, 13.9) in group D, with GMT ratio of 7.6 (95% CI: 4.1, 14.1). There was a 6.3-fold (GMTs, 45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against Delta and Omicron variants in group A, respectively, compared with group B. However, there was no significant difference between group C and group D. Both heterologous and homologous booster immunizations were safe and well tolerated. Conclusions and RelevanceHeterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boost, without increasing safety concerns. Trial RegistrationClinicalTrials.gov NCT04952727 Key Points QuestionDoes a heterologous immunization with recombinant adenovirus type 5-vectored vaccine (Convidecia) produced a non-inferior or superior response of neutralizing antibodies among elderly primed with two doses of inactivated COVID-19 vaccine (CoronaVac), compared to the homologous boosting FindingsIn this randomized clinical trial, a heterologous third dose of Convidecia resulted in a 6.2-fold (geometric mean titers: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against wild-type strain, Delta and Omicron variants 14 days post boosting, respectively, compared to the homologous boost with CoronaVac MeaningHeterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boosting.
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BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Subject(s)
Animals , Humans , Mice , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral , Hemagglutinins , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H3N2 Subtype , Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Influenza in Birds , Influenza, Human/prevention & controlABSTRACT
BackgroundThe safety and immunogenicity of heterologous prime-boost COVID-19 vaccine regimens with one shot of a recombinant adenovirus type-5-vectored COVID-19 vaccine Convidecia has not been reported. MethodsWe conducted a randomized, controlled, observer-blinded trial of heterologous prime-boost immunization with CoronaVac and Convidecia in healthy adults 18-59 years of age. Eligible participants who were primed with one or two doses of CoronaVac were randomly assigned at a 1:1 ratio to receive a booster dose of Convidecia or CoronaVac. Participants were masked to the vaccine received but not to the three-dose or two-dose regimen. The occurrences of adverse reactions within 28 days after the vaccination were documented. The geometric mean titers of neutralizing antibodies against live SARS-CoV-2 virus were measured at 14 and 28 days after the booster vaccination. ResultsBetween May 25 and 26, 2021, a total of 300 participants were enrolled. Participants who received a booster shot with a heterologous dose of Convidecia reported increased frequencies of solicited injection-site reactions than did those received a homogeneous dose of CoronaVac, but frequencies of systemic reactions. The adverse reactions were generally mild to moderate. The heterologous immunization with Convidecia induced higher live viral neutralizing antibodies than did the homogeneous immunization with CoronaVac (197.4[167.7, 232.4] vs. 33.6[28.3, 39.8] and 54.4[37. 9, 78.0] vs. 12.8[9.3, 17.5]) at day 14 in the three- and two-dose regimen cohort, respectively. ConclusionsThe heterologous prime-boost regimen with Convidecia after the priming with CoronaVac was safe and significantly immunogenic than a homogeneous boost with CoronaVac (ClinicalTrials.gov, number NCT04892459).
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The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the healthcare measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride), which may be used as potential inhibitor of currently circulating highly pathogenic coronaviruses - SARS-CoV-2 and MERS-CoV.
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The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both 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. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. 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 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.
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Objective@#To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years.@*Methods@#Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis.@*Results@#A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49% (95%CI: 40%-57%). Subgroup analysis found that the protection rate of LAIV was 35% against influenza A (H1N1) pdm09 (95%CI: 5%-56%), 35% against influenza A (H3N2) (95%CI: 21%-46%), and 71% against influenza B (95%CI: 55%-82%). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56% (95%CI: 48%-63%) and 44% (95%CI: 27%-57%), respectively. The protection rates of LAIV in Europe and North America were 65% (95%CI: 47%-77%) and 46% (95%CI: 36%-55%), respectively.@*Conclusion@#LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.
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There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 μg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.
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Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.
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Original antigenic sin may exist in the influenza virus infection or vaccination, which possibly reduces the protective efficacy in repeated influenza vaccination. This paper reviews the literature on the original antigenic sin and its influence in influenza vaccination, and interprets the possible mechanism of this phenomenon from the three aspects of influenza virus structure, humoral immunity and cellular immunity. A large number of studies have shown that original antigen sin has a negative impact on influenza vaccination, but the evidence disproveing this phenomenon also exist, so multi-center large-scale clinical trials should be conducted to provide evidence-based basis for reaearching whether original antigen sin exists and its effects. in order to provide reference for the development and update of noval influenza vaccines and its formulation of immunization strategies.
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Objective@#To construct a method to express ScFv antibody from PCR products, and use it in phage display for high-throughput ScFv expression.@*Methods@#Cytomegalovirus (CMV) promotor, ScFv and BGH-Poly A gene fragments were amplified by PCR. Overlapping PCR was used to form a tandemly linear cassette gene. By transiently transfected into 293T cells, ScFv antibodies expression of cassette gene were tested by Western blot, enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent antibody (IFA). Ninety-six clones of antibody genes in phage library were selected and expressed by cassette expression system. The expression level was evaluated and analyzed.@*Results@#Three fragments were obtained and a cassette expression system formed. Cassette expression system worked successfully in 293T cells, as a Mr.38×103 brand could observed in Western blot assay. The expressed antibody could specifically bind to its antigen by result of ELISA and IFA. This cassette expression system could also be used in phage display for high-throughput panning.@*Conclusions@#The cassette expression system was constructed successfully and high-throughput antibody expression has been achieved.
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Maternal immunization is an immune strategy that protects both mothers and early-life infants from disease by the vaccination of pregnant women. The effect of maternal immunization is influenced by the types of vaccines, the timing of vaccination, the subtypes of antibodies induced by vaccines, and the health status of mothers themselves. Inactivated influenza vaccination during pregnancy and DPT vaccination during the third trimester of pregnancy have been widely used in the world, while Hepatitis B vaccine, pneumococcal and meningococcal vaccines also show good efficacy and safety in pregnant women. This article reviews the research progress of Maternal Immunization in order to provide a reference for Maternal Immunization planning and policymaking in China.
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Genes play an important role in the immune system response,and different gene loci may result in different vaccine immune response rates.This review focuses on the correlation between gene polymorphisms and vaccine immune response in order to investigate the influence of gene polymorphisms on the immune response to vaccines.It discusses the effect of an individual's immune response after vaccination at genetic level and provides a scientific basis for individualized immune development strategies.It reveals that human leukocyte antigen genes,various cytokines and their receptor genes,and Toll-like receptor genes all affect the vaccine immune response.
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The importance of vaccine on public health is related to the herd protection related to the levels of vaccine coverage,which directly influences the vaccinated individuals as well as the unvaccinated community.Reaching the level of herd protection by increasing vaccine coverage is the basic strategy to eradicate related infectious diseases.Again,herd protection has played an important role in public health practices.With the increasing interests in estimating the vaccine herd protection,we however,have seen only few relevant papers including observational population-based and cluster-randomized clinical trials reported in China.We hope to discuss the study designs for evaluating the vaccine herd protection in order to generate evidence-based related research in this field.
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Due to the tumor malignancy or immunosuppressive treatment,patients with cancer in general are more susceptible to vaccine-preventable infections.The types,timing,dose of vaccination or even the immunization program for them may differ from those for the normal persons.At present,it is recommended to use inactivated vaccines for patients with cancer rather than attenuated live vaccines,Vaccinations should be avoided during immunosuppressive therapy;patients with cancer should receive double dosage of hepatitis B vaccines and two doses of inactivated influenza vaccines yearly.This paper summarizes the progress in clinical trials of vaccination for cancer patients in foreign countries,and provide reference for the development and implementation of vaccination strategy for cancer patients in China.
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Genes play an important role in the immune system response,and different gene loci may result in different vaccine immune response rates.This review focuses on the correlation between gene polymorphisms and vaccine immune response in order to investigate the influence of gene polymorphisms on the immune response to vaccines.It discusses the effect of an individual's immune response after vaccination at genetic level and provides a scientific basis for individualized immune development strategies.It reveals that human leukocyte antigen genes,various cytokines and their receptor genes,and Toll-like receptor genes all affect the vaccine immune response.
ABSTRACT
The importance of vaccine on public health is related to the herd protection related to the levels of vaccine coverage,which directly influences the vaccinated individuals as well as the unvaccinated community.Reaching the level of herd protection by increasing vaccine coverage is the basic strategy to eradicate related infectious diseases.Again,herd protection has played an important role in public health practices.With the increasing interests in estimating the vaccine herd protection,we however,have seen only few relevant papers including observational population-based and cluster-randomized clinical trials reported in China.We hope to discuss the study designs for evaluating the vaccine herd protection in order to generate evidence-based related research in this field.
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Due to the tumor malignancy or immunosuppressive treatment,patients with cancer in general are more susceptible to vaccine-preventable infections.The types,timing,dose of vaccination or even the immunization program for them may differ from those for the normal persons.At present,it is recommended to use inactivated vaccines for patients with cancer rather than attenuated live vaccines,Vaccinations should be avoided during immunosuppressive therapy;patients with cancer should receive double dosage of hepatitis B vaccines and two doses of inactivated influenza vaccines yearly.This paper summarizes the progress in clinical trials of vaccination for cancer patients in foreign countries,and provide reference for the development and implementation of vaccination strategy for cancer patients in China.
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Due to immature development of the immune system, preterm infants are at increased risk of infections from vaccine-preventable diseases. But at the same time, premature vaccination may not induce a good immune response because of the incomplete development of the neonatal immune system, and may cause serious adverse reactions risk due to the poor immune tolerance, thus vaccination of preterm infants at the appropriate time is the key to reducing the risk of infectious disease and obtaining vaccine protection. At present, it is generally recommended that the gestational age and birth weight should be considered in the vaccination of preterm infants. The timing, type and even the immunization schedule of the vaccine should be differ from that of the full term infants. However, there is a lack of research results and data on immunization program in preterm infants in China, and there is still no provided universal guidelines for their vaccine immunization. This article aims to summarize the guidelines and clinical trials of vaccination of preterm infants in foreign countries, and to provide reference for the formulation and implementation of immunization strategies for preterm infants in China.
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Objective@#To disclose the effects of booster immunization of human diploid cell rabies vaccine (HDCV) after eight years of primary vaccination.@*Methods@#Sixty subjects who had participated the phase Ⅲ clinical trial of freeze-dried HDCV were selected and gaven booster immunization after eight years of primary vaccination. The side effects of booster immunization were observed. The serum before and after 14 days of booster immunization were collected and detected the rabies virus neutralizing antibody (RVNA) by rapid fluorescent focus inhibition test (RFFIT). The positive rate and geometric mean titer (GMT) of RVNA before and after booster immunization were made statistical analysis.@*Results@#Total 54 subjects finished the follow-up and RVNA detection. No sever side-effects were observed in 30 min or 15 days of follow-up after booster immunization. The positive rate of RVNA before and after booster immunization were 51.85% (28/54) and 96.30% (52/54). The GMT of RVNA before and after booster immunization were 1.42 IU/ml and 30.61 IU/ml.@*Conclusions@#The freeze-dried HDCV has good immune effects with one-dose of booster immunization after eight years of primary vaccination.
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Intestinal microbiota plays an important role in the development of immune system,es-pecially in the formation of immune response. Immune response to vaccination varies with region and popula-tion,which may be related to the differences in intestinal microbiota. This review focused on the correlation between intestinal microbiota and immune response to vaccination in order to find a new way to enhance vac-cine-induced immune response. It was revealed that intestinal microbiota might be involved in the immune responses to vaccines against rotavirus, typhoid and polio. Although probiotics, prebiotics and synbiotics could not significantly enhance vaccine-induced immune response,they might have a beneficial effect on vac-cine by regulating intestinal microbiota.
