Nanoparticle-based multivalent human antibodies offer potent and broad neutralization against Omicron sublineages

Dear Editor As of January 2023,coronavirus disease 2019(COVID-19)induced by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused more than 6.7 million deaths,with SARS-CoV-2 variants continuing to alter the trajectory of the COVID-19 pandemic.Indeed,the prevalence of the newly emergent Omicron sublineages,particularly BA.4/5 and XBB,has highlighted the critical need for the design and production of broadly potent neutralization antibodies to efficiently combat SARS-CoV-2 variants.Neutralizing antibodies(nAbs)XMA01,XMA04,and XMA09,which target noncompeting antigenic sites in RBD(receptor binding domain),exhibit high neutralization potency against earlier disease variants(Supplementary Fig.1a–d),as previously reported by us.

Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects

Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years,but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone.In this study,an oncolytic virus(rVSV-LCMVG)that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells.By transforming the immunosuppressive tumor microenvironment into an immunosensitive one,in B16 tumor-bearing mice,combination therapy showed superior antitumor effects than monotherapy.This occurred whether the OV was administered intratumorally or intravenously.Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8^(+)T cells to the TME to trigger antitumor immune responses.Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment,downregulating the expression of PD-1,and restoring effector T-cell function.To offer a combination therapy with greater translational value,mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells.The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival.This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens,in terms of synergistic efficacy and mechanism.

Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness.To experimentally demonstrate the epidemiological results,we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2.Remarkably,high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss,weakness,piloerection,hunched back and abdominal respiration,as well as severe pneumonia,pulmonary edema,consolidation,and fibrosis.In contrast with the males,the female hamsters showed much lower shedding viral titers,moderate symptoms,and relatively mild lung pathogenesis.The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.

Persisting lung pathogenesis and minimum residual virus in hamster after acute COVID-19

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 200 million people,causing coronavirus disease 2019(COVID-19)worldwide.Lungs are the primary target organ of SARS-CoV-2 infection.The mild COVID-19 cases develop symptoms of fever,fatigue,muscle weakness,chest pain,headache and cough(Chen et al.,2020;Wang et al.,2020;Zhu et al.,2020),while severe COIVD-19 cases might have pneumonia,breathing difficulties,multiple organ failure and death(Chen et al.,2020;Wang et al.,2020;Zhu et al.,2020).Both the clinicians and researchers have largely focused on the acute phase of COVID-19,but the long-term health consequences of the COVID-19 patients after clinical recovery remain less investigated.Several clinical cohorts demonstrated that some patients discharged from hospital still experience symptoms including fatigue,muscle weakness,chest pain,cough and breathing difficulties(Carfi et al.,2020;Lim et al.,2020;Huang et al.,2021).Moreover,severely impaired pulmonary diffusion capacities and abnormal chest imaging manifestations were observed in some convalescent patients(Huang et al.,2021).Surprisingly,residual virus(An et al.,2020;Yao et al.,2020;Kim et al.,2021)were detected in some convalescent patients.

Infection,pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile,adult and aged Syrian hamsters

The new predominant circulating SARS-CoV-2 variant,Omicron,can robustly escape current vaccines and neutralizing antibodies.Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants,its pathogenicity in different age groups has not been well elucidated.Here,we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters,with more body weight loss,respiratory tract viral burden,and lung injury in these hamsters than in adult hamsters.Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection,whereas aged hamsters show excessive proinflammatory cytokine expression,delayed viral clearance,and aggravated lung injury.Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters.Overall,the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

Development of a fluorescent probe hydrolysis-insulated isothermal PCR for rapid and sensitive on-site detection of African swine fever virus

Dear Editor,African swine fever virus(ASFV),the sole member of the family Asfarviridae,is the causative agent of African swine fever(ASF),a viral disease that leads to high mortality in domestic pigs.Since firstly identified in Kenya in the 1920s,ASFV has been prevalent in Africa,Europe,and Russian Federation(Sanchez et al.,2019).Recently,ASFV was introduced to Asian countries including China,Mongolia,Vietnam,Cambodia,Laos and South Korea,which lead to huge economic losses to local pig industries(Li and Tian,2018;Gaudreault and Richt,2019).The first case of ASFV in China was reported in August 2018(Zhou et al.,2018).

New discovery of high-affinity SARS-CoV-2 spike S2 protein binding peptide selected by PhIP-Seq

Dear Editor,Theworld had suffered pandemics of COVID-19 caused by SARS-CoV-2.At the time ofwriting,COVID-19 is still widely spreading inmany countries and regions,and by June 14,2022,totally 532,887,351 cases,including 6,307,021 deaths,were reported globally(WHO,https://covid19.who.int/table).Powerful measures,such as prophylactic and therapeutic interventions against the virus,are in urgent need for COVID-19 control and prevention.The spike protein,which is expressed on the virus surface,is the key determinant of viral-host interaction(Ng et al.,2021)and mediates the virus entry.