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PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mrna tumor vaccines

Chinese Chemical Letters 2024年第5期35卷 314-319页

作者： Wen Xiao Fazhan Wang Yangzhuo Gu Xi He Na Fan Qian Zheng Shugang Qin Zhongshan He Yuquan Wei Xiangrong Song Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450000China

Dendritic cell(DC)-targeted delivery of mrna is a prominent method to boost the efficacy of mrna tumor *** targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mrna delivery *** the PEG linker length influences the targeting delivery efficiency of mrna nanocarrier in vivo remains ***,we designed and constructed DC-targeted mrna delivery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP_(400)-LPX(the linker was PEG400)showed the optimal mrna expression and antigen presentation owing to the highly efficient uptake by ***,MP_(400)-LPX could better inhibited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse ***,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mrna *** findings provided a new platform for the rational design of targeted mrna nanovaccines with shorter-length PEG.

关键词： Cancer immunotherapy mrna vaccines DC-targeted delivery PEGylated liposomes Cellular uptake

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Covid-19 Mutations and the Effect of Different vaccines on Immune Memory

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Journal of Endocrinology Research 2021年第1期3卷 32-40页

作者： Xanya Sofra City University LondonNew School for Social ResearchNew Yorkthe United States

We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and *** their close kinship,SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions,and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.A single amino acid substitution such as replacing Aspartate(D)with Glycine(G)composes the D614G mutation that is around 20%more infectious than its predecessor *** B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid *** examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions *** previous versions of coronavirus,where random mutations eventually precipitate extinction,the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious,facilitating its ability to evade detection,thus challenging the effectiveness of a large variety of emerging *** enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein,restricting the virus from releasing its contents into the *** antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I,compromising adaptive efficiency to recognize the virus,possibly provoking a cytokine storm that injures vital *** respect to that perspective,the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mrna version,the Adenovirus DNA,Spike protein subunits,the deactivated virus genres,or,finally,the live attenuated coronavirus that a

关键词： SARS-CoV2 Covid-19 mrna vaccines DNA vaccines Inactivated virus vaccines Covid-19 mutations D614G B117 P1 501Y.V2 Immune memory Spike protein

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vaccines’ Safety and Effectiveness in the Midst of Covid-19 Mutations

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Health 2021年第3期13卷 283-298页

作者： Xanya Sofra City University London UK New School for Social Research New York USA

We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mrna version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.

关键词： SARS-CoV2 Covid-19 mrna vaccines DNA vaccines Inactivated Virus vaccines Covid-19 Mutations D614G B117 P1 501Y.V2 Immune Memory Spike Protein

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Myocarditis and pericarditis following mrna vaccination in autoimmune inflammatory rheumatic disease patients: A single‐center experience

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Rheumatology & Autoimmunity 2022年第2期2卷 92-97页

作者： Shreeya Patel Emma Wu Maninder Mundae Keith Lim Department of Rheumatology Western HospitalFootscrayVictoriaAustralia

Introduction:The mrna vaccines Comirnaty(Pfizer/BioNTech)and Spikevax(Moderna)are considered safe and highly effective against SARS‐***,they are also associated with a small increased risk of pericarditis and *** is concern about an increased risk of these complications in patients with autoimmune inflammatory rheumatic diseases(AIRD).Case Report:We describe three patients with pre‐existing AIRD who developed myocarditis or pericarditis shortly after receiving their first dose of the Pfizer‐BioNTech *** first case is a 31‐year‐old female with systemic lupus erythematosus(SLE)and anti‐phospholipid syndrome(APLS)who presented 7 days after receiving the Pfizer‐BioNTech vaccine and was diagnosed with myopericarditis following a positive troponin and abnormal transthoracic echocardiogram(TTE).The second case is a 29‐year‐old man with seronegative inflammatory arthritis and APLS who presented 7 days after receiving the first dose of the Pfizer‐BioNTech *** troponin and TTE were unremarkable however his ECG showed widespread ST ***,the third case is a 34‐year‐old man with Behcet's disease with a history of recurrent *** developed a recurrence of symptoms approximately 7 days after his Pfizer‐BioNTech vaccine and self‐commenced prednisolone at *** had normal laboratory and radiological *** patients received prednisolone resulting in a quick recovery and resolution of ***:In this review we discuss the association between myocarditis,pericarditis and mrna COVID‐19 vaccines,those who are at greatest risk and current clinical *** also discuss the possible increased risk in AIRD patients and the current research supporting this.

关键词： mrna vaccines myocarditis pericarditis severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)

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