Genomic Characterization of a Streptococcus suis Serotype 2 Isolated from a Human Patient

Streptococcus suis(S. suis) is a Gram-positive zoonotic pathogen. S. suis infection in humans commonly causes meningitis, septicemia, arthritis,and streptococcal toxic shock-like syndrome(STSLS). S. suis has 29 serotypes, of which S. suis serotype 2(SS2) has the highest clinical isolation rate and strongest pathogenicity and causes most S. suis human infections.About 1,000 different sequence types(STs)were identified in S.suis based on multilocus sequence typing(MLST).Among these,STs,ST1,and ST7 belong to serotype 2 and are the major hazards of S.suis.in 1998 and 2005,two cases of SS2 human infection outbreak were reported in Jiangsu and Sichuan,China,causing 14 deaths and 38 deaths,respectively.

Next Steps for Efficacy Evaluation in Clinical Trials of COVID-19 Vaccines

1.Introduction A vaccine clinical trial examines the effects of a vaccine on human volunteers in terms of safety,immunogenicity,and clinical efficacy through three distinct stages[1].In general,phase 1 studies focus on safety and reactogenicity,while phase 2 studies attempt to establish an immunogenicity proof of dose range,dosage,and immunization procedure(sometimes even efficacy data).Large phase 3 studies are designed to evaluate whether the dosing and vaccination schedule can deliver the desired protection efficacy with an acceptable safety profile[2].A phase 3 vaccine clinical trial provides indispensable efficacy data to support a vaccine that has been issued with licensure.

Characterization of whole genomes from recently emerging Mpox cases in several regions of China,2023

Dear Editor,Mpox(formerly known as monkeypox)is a zoonotic disease caused by infection with the monkeypox virus(MPXV).Mpox cases have been sporadic over the past few decades,with outbreaks occurring in only a limited number of countries,primarily as a result of imported cases(El Eid et al.,2022;Tan and Gao,2022).

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials

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 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/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:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg 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-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg 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 seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced 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-mg 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).

Safety and immunogenicity of a recombinant COVID-19 vaccine(Sf9 cells)in healthy population aged 18 years or older:two single-center,randomised,double-blind,placebo-controlled,phase 1 and phase 2 trials

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply.We did two singlecenter,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%Cl 61.9-171.2)and 102.6(95%Cl 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.

Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2

Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COVID-19).As a newly emerged member of the coronavirus family,SARS-CoV-2 is an enveloped positive-strand RNA virus,which has probably the largest genome(approximately 30 kb)among all RNA viruses.The nucleocapsid(N)protein of SARS-CoV-2 is mainly responsible for recognizing and wrapping viral RNA into helically symmetric structures(Malik,2020).

Immunological surrogate endpoints of COVID-2019 vaccines:the evidence we have versus the evidence we need

lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an unparalleled speed.Theavailability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates,which is crucial to control COVID-19 pandemic.Several phase 3 efficacy trials of COVID-19 vaccine candidates are underway,which provide opportunities for the determination of COVID-19 correlates of protection.In this paper,we review currentknowledge for existence of COVD-19 correlates of protection,methods for assessment of immune correlates of protection andissues related to COVID-19 correlates of protection.

Coronavirus disease 2019 vaccines:landscape of global studies and potential risks

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.

A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9

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 microneutralizationin 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(TCID_(50))of H7N9 virus(influenza A/Nanjing/1/2013)invitro,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.

Challenges of COVID-19 vaccination in patients with cancer

Patients with cancer are at increased risk of SARA-CoV-2 infection or developing severe COVID-19 cases due to malignancy or immunosuppressive therapy,but they are generally excluded from the target population for COVID-19 vaccination.In general,inactivated vaccines are safe and immunogenic for patients with cancer,but live attenuated vaccines are not recommended.The study suggested that the safety of the mRNA COVID-19 vaccine in patients with cancer is similar to that in healthy people,but immunogenicity is slightly weaker,and a booster dose may be needed.This paper aims to summarize the results of COVID-19 vaccine clinical studies conducted in patients with cancer worldwide and the relevant guidelines released by authorities,so as to provide evidence for promoting COVID-19 vaccination for patients with cancer.

Verification of SARS-CoV-2-encoded small RNAs and contribution to infection-associated lung inflammation

To the Editor:Severe_acute_respiratory,syndrome coronavirus 2(SARS-CoV-2)is the virus causing coronavirus disease2019(COVID-19).[1]As anewevolutionary branch within coronaviruses,SARS-CoV-2 contains around 29.8 kilobase and shows 79.2%identity with SARS-CoV-1.

Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS:a multicenter randomized controlled trial

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell(hUC-MSC)infusion for immune nonresponder(INR)patients with chronic HIV-1 infection,who represent an unmet medical need even in the era of efficient antiretroviral therapy(ART).Seventy-two INR patients with HIV were enrolled in this phase II randomized,double-blinded,multicenter,placebo-controlled,dose-determination trial(NCT01213186)from May 2013 to March 2016.They were assigned to receive high-dose(1.5 x 106/kg body weight)or low-dose(0.5 x 106/kg body weight)hUC-MSC,or placebo.Their clinical and immunological parameters were monitored during the 96-week follow-up study.We found that hUC-MSC treatment was safe and well-tolerated.Compared with baseline,there was a statistical increase in CD4+T counts in the high-dose(P<0.001)and low-dose(P<0.001)groups after 48-week treatment,but no change was observed in the control group.Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group(95.8%vs.70.8%,P=0.00A).However,no significant changes in CD4/CD84-T counts and CD4/CD8 ratios were observed among the three groups.In summary,hUC-MSC treatment is safe.However,the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.

COVID-19 in children:epidemic issues and candidate vaccines

A large-scale vaccination of coronavirus disease-19(COVID-19)in adults has been conducted for nearly a year,and there is a growing recognition that immunization for children is also essential.It has been months since emergency use of pediatric COVID-19 vaccine was approved,we reviewed the prevalence and transmission of COVID-19 in children.The prevalence of COVID-19 in children is reduced due to vaccination even in a Delta prevalent period,so an increase in the vaccination rate is needed in children.Although the precise role of children in the transmission requires more research to uncover,they likely played a significant role,according to the available literature.We also described four candidate COVID-19 vaccines for children on their safety and immunogenicity and the impact of severe acute respiratory syndrome coronavirus 2 variants on childhood vaccination.Safety issues on pediatric vaccines post-approval,like adverse events following immunization and adverse events of special interest require studies on long-term and effective regulatory mechanisms.

IL-33 in COVID-19: friend or foe?

The COVID-19 pandemic,caused by the highly transmissible and pathogenic severe acute respiratory syndrome coronavirus 2(SAR-CoV-2),has led to more than 2.7 million deaths worldwide as of March 2021.Although considerable efforts are underway to reveal the immunopathology of COVID-19,the key factors and processes that initiate hyperinflammatory responses and cause severe clinical outcomes in certain individuals remain unclear.The damage-associated molecular pattern(DAMP)molecule IL-33 belongs to the IL-1 family and has been recognized as an alarmin that indicates cellular damage or infection.Full-length IL-33 requires cleavage by proteases to generate its mature bioactive form,which can bind to the ST2 receptor(also known as IL-1RL1),leading to activation of the NF-κB pathway in various innate and adaptive immune cells.The relatively high abundance of IL-33 in epithelial and endothelial cells accounts for its proinflammatory role in respiratory diseases.1 Recent observations have revealed that serum IL-33 is upregulated in elderly patients with COVID-19 and associated with adverse outcomes.

The COVID-19 Vaccine in Clinical Trials: Where Are We Now?

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to scale up around the world, costing severe health and economic losses. The development of an effective COVID-19 vaccine is of utmost importance. Most vaccine designs can be classified into three camps: protein based (inactivated vaccines, protein subunit, VLP and T-cell based vaccines), gene based (DNA or RNA vaccines, replicating or non-replicating viral/bacterial vectored vaccines), and a combination of both protein-based and gene-based (live-attenuated virus vaccines). Up to now, 237 candidate vaccines against SARS-CoV-2 are in development worldwide, of which 63 have been approved for clinical trials and 27 are evaluated in phase 3 clinical trials. Six candidate vaccines have been authorized for emergency use or conditional licensed, based on their efficacy data in phase 3 trials. This review summarizes the strengths and weaknesses of the candidate COVID-19 vaccines from various platforms, compares, and discusses their protective efficacy, safety, and immunogenicity according to the published clinical trials results.