Innovation-driven trend shaping COVID-19 vaccine development in China

Confronted with the Coronavirus disease 2019(COVID-19)pandemic,China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)transmission and mutation,with several innovative platforms,which provides various technical means in this persisting combat.Derived from collaborated researches,vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19.Herein,we outline representative vaccines in multiple routes,while the merits and plights of the existing vaccine strategies are also summarized.Likewise,new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants.All in all,with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease,alongside the traditional routes,the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

Passive antibody therapy in emerging infectious diseases

The epidemic of corona virus disease 2019(COVID-19)caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern(VOCs)has been ongoing for over 3 years.Antibody therapies encompassing convalescent plasma,hyperimmunoglobulin,and neutralizing monoclonal antibodies(mAbs)applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment.In this review,the development path,action mechanism,clinical research results,challenges,and safety profile associated with the use of COVID-19 convalescent plasma,hyperimmunoglobulin,and mAbs were summarized.In addition,the prospects of applying antibody therapy against VOCs was assessed,offering insights into the coping strategies for facing new infectious disease outbreaks.

Non-small cell lung cancers(NSCLCs)oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors

With the continuous in-depth study of the interaction mechanism between viruses and hosts,the virus has become a promising tool in cancer treatment.In fact,many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy.Human enterovirus is one of the most convenient sources to generate oncolytic viruses,however,the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants:a randomized phase 2 trial

An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.

Early assessment of the safety and immunogenicity of a third dose(booster)of COVID-19 immunization in Chinese adults

Inducing durable and effective immunity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)via vaccination is essential to combat the current pandemic of coronavirus disease 2019(COVID-19).It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time,which calls for an additional vaccination regime,as known as booster immunization,to restore immunity among previously vaccinated populations.Here we report a pilot open-label trial of a third dose of BBIBP-CorV,an inactivated SARS-CoV-2 vaccine(Vero cell),on 136 participants aged between 18 to 63 years.Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28.While systemic reactogenicity was either absent or mild,SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks,surpassing the peak antibody titers elicited by the initial two-dose immunization regime.Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination.Furthermore,in an exploratory study,a newly developed recombinant protein vaccine,NVSI-06-08(CHO Cells),was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals.Together,these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity,providing support for further trials of booster vaccination in larger populations.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV:a phase 2 trial

The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine(BBIBP-CorV)followed by a recombinant protein-based vaccine(NVSI-06-07),using homologous boost with BBIBP-CorV as control.Three groups of healthy adults(600 individuals per group)who had completed two-dose BBIBP-CorV vaccinations 1–3 months,4–6 months and≥6 months earlier,respectively,were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.Immunogenicity assays showed that in NVSI-06-07 groups,neutralizing antibody geometric mean titers(GMTs)against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination,whereas only 4.20–16.78 folds of increases were observed in control groups.For Omicron variant,the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14,however,a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster.Similar results were obtained for other SARS-CoV-2 variants of concerns(VOCs),including Alpha,Beta and Delta.Both heterologous and homologous boosters have a good safety profile.Local and systemic adverse reactions were absent,mild or moderate in most participants,and the overall safety was quite similar between two booster schemes.Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs,including Omicron.

Efficacy,safety and immunogenicity of hexavalent rotavirus vaccine in Chinese infants

A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.

A novel inactivated whole-cell Pseudomonas aeruginosa vaccine that acts through the cGAS-STING pathway

Pseudomonas aeruginosa infection continues to be a major threat to global public health,and new safe and efficacious vaccines are needed for prevention of infections caused by P.aeruginosa.X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P.aeruginosa infection.However,the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation.Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P.aeruginosa by boosting T cells.The aim of the present study was to further explore the immunological mechanisms of the vaccine.Herein,P.aeruginosa PAO1,a widely used laboratory strain,was utilized to prepare the vaccine,and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1(XPa).By detecting CD86,CD80,and MHCII expression,we found that XPa fostered dentritic cell(DC)maturation by detecting.XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro,and DC finally underwent apoptosis and pyroptosis after XPa stimulation.In addition,DC stimulated by XPa induced CD8+T-cell proliferation in vitro and generated immunologic memory in vivo.Moreover,XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection.XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9.Chronic obstructive pulmonary disease(COPD)mice immunized with XPa could resist PAO1 infection.Therefore,a new mechanism of an X-ray-inactivated whole-cell vaccine against P.aeruginosa infection was discovered in this study.

Type I IFN deficiency:an immunological characteristic of severe COVID-19 patients

Recently,a paper published in Science by Hadjadj et al.reported that type I interferon(IFN)deficiency,could be a hallmark of severe coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Severe COVID-19 was also associated with a lymphocytopenia,persistent blood viral load,and an exacerbated inflammatory response(Fig.1).These findings provide insights into the treatment of severe COVID-19 patients with type I IFN.

Cellular tropism and antigenicity of mink-derived SARS-CoV-2 variants

Dear Editor,The outbreak of SARS-CoV-2 in minks has been observed recently,raising serious concerns over cross-species transmission and the emergence of variants capable of rendering antibody therapy and vaccines less effective.Here,the species tropism and antigenicity of the spike protein of ten variants were analyzed in pseudovirus-based assays involving 25 cell lines as well as 293T cells expressing ACE2 receptor from 14 species.