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

We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.Despite 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 614D.The B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid exchange.We examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions involved.Unlike 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 vaccines.Vaccination 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 cell.Developing 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 organs.With 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 appears to demonstrate the greatest effectiveness,yet,encompass a relatively higher risk.

Clonal Strategy Algorithm Based on the Immune Memory

Based on the clonal selection theory and immune memory mechanism in the natural immune system, a novel artificial immune system algorithm, Clonal Strategy Algorithm based on the Immune Memory （CSAIM）, is proposed in this paper. The algorithm realizes the evolution of antibody population and the evolution of memory unit at the same time, and by using clonal selection operator, the global optimal computation can be combined with the local searching. According to antibody-antibody （Ab-Ab） affinity and antibody-antigen （Ab-Ag） affinity, the algorithm can allot adaptively the scales of memory unit and antibody population. It is proved theoretically that CSAIM is convergent with probability 1. And with the computer simulations of eight benchmark functions and one instance of traveling salesman problem （TSP）, it is shown that CSAIM has strong abilities in having high convergence speed, enhancing the diversity of the population and avoiding the premature convergence to some extent.

Optimization of virtual machine placement based on constrained immune memory and immunodominance clone in IaaS cloud mode equipment training

In infrastructure as a service(IaaS)cloud mode equipment simulated training,to keep the resource utilization ratio in a rational high level,improve the training effect and reduce the system running cost,the problem of training virtual machine(TVM)placement needs to be resolved first.We make analysis to the problem and give the mathematical formulation to the problem.Then,we figure out the principle and target of the TVM placement.Based on above analysis,we propose a constrained immune memory and immunodominance clone(CIMIC)TVM placement optimization algorithm.By reverse optimization of the initial antibody population,the searching range is reduced.The common antibody population and the immunodominance antibody population evolve simultaneously,which realizes the simultaneous progressing of global searching and local searching of solutions.Further,local optimal is avoided by this means.Memory antibody makes ful use of the unfeasible solutions and the diversity of antibody population is maintained.The constraint information of the problem is utilized to improve the optimization effect.Experiment results show that the CIMIC algorithm improves the overall optimization effect of TVM placement,reduces the server number and improves the resource utilization and system stability.

Temporal pattern of humoral immune response in mild cases of COVID-19

BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporality of reinfection,provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and consequently helps in global public health and vaccination strategy.Among the patients who became infected with SARS-CoV-2,the majority who did not progress to death were those who developed the mild COVID-19,so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G(IgG)in mild cases of COVID-19.METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction(RT-qPCR)-positive volunteers from the municipality of Toledo/Paraná/Brazil,underwent two distinct serological tests,enzyme-linked immunosorbent assay,and detection of anti-nucleocapsid IgG.Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021.All assays were performed in duplicate and the manufacturers'recommendations were strictly followed.The data were statistically analyzed using multiple logistic regression;the variables were selected by applying the P<0.05 criterion.RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo.The time periods when the highest number of participants with detectable IgG was observed were 1,2 and 3 mo.It was observed that 9.42%of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57%were also IgG negative at less than 1 mo.At 5 mo,3.14%of volunteers were IgG negative,and at 6 or 7 mo,1 volunteer(0.52%)had no detectable IgG.During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study,no statistical significance was observed for any association analyzed.Moreover,considering the age category between 31 and 59 years as the exposed group,the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older,showing that in both age categories there was no association between the pair of variables analyzed.Regarding chronic disease,the exposure group consisted of the participants without any comorbidity,so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.CONCLUSION A temporal pattern of IgG response was not observed,but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.

Immunological aspects of COVID-19:What do we know?

The newly emerged coronavirus(severe acute respiratory syndrome coronavirus 2 SARS-CoV-2)and the disease that it causes coronavirus disease 2019(COVID-19)have changed the world we know.Yet,the origin and evolution of SARS-CoV-2 remain mostly vague.Many virulence factors and immune mechanisms contribute to the deteriorating effects on the organism during SARS-CoV-2 infection.Both humoral and cellular immune responses are involved in the pathophysiology of the disease,where the principal and effective immune response towards viral infection is the cell-mediated immunity.The clinical picture of COVID-19,which includes immune memory and reinfection,remains unclear and unpredictable.However,many hopes are put in developing an effective vaccine against the virus,and different therapeutic options have been implemented to find effective,even though not specific,treatment to the disease.We can assume that the interaction between the SARS-CoV-2 virus and the individual's immune system determines the onset and development of the disease significantly.

The Motif Tracking Algorithm

The search for patterns or motifs in data represents a problem area of key interest to finance and economic researchers. In this paper, we introduce the motif tracking algorithm （MTA）, a novel immune inspired （IS） pattern identification tool that is able to identify unknown motifs of a non specified length which repeat within time series data. The power of the algorithm comes from the fact that it uses a small number of parameters with minimal assumptions regarding the data being examined or the underlying motifs. Our interest lies in applying the algorithm to financial time series data to identify unknown patterns that exist. The algorithm is tested using three separate data sets. Particular suitability to financial data is shown by applying it to oil price data. In all cases, the algorithm identifies the presence of a motif population in a fast and efficient manner due to the utilization of an intuitive symbolic representation. The resulting population of motifs is shown to have considerable potential value for other applications such as forecasting and algorithm seeding.

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

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.

Vaccines and autoimmunity during the COVID-19 pandemic

To control the pandemic,efficient vaccines must be applied to the population,including patients with autoimmune diseases.Therefore,one can expect that coronavirus disease 2019(COVID-19)vaccines may influence the underlying autoimmune processes in these patients.Additionally,it is essential to understand whether COVID-19 vaccines would be effective,safe,and provide long-lasting immunological protection and memory.However,the currently available and approved COVID-19 vaccines turned out to be safe,effective,and reliable in patients with autoimmune inflammatory and rheumatic diseases.Furthermore,most patients said they felt safer after getting vaccinations for COVID-19 and reported enhanced overall quality of life and psychological wellbeing.In general,the COVID-19 vaccines have been highly tolerated by autoimmune patients.Such findings might comfort patients who are reluctant to use COVID-19 vaccines and assist doctors in guiding their patients into receiving vaccinations more easily and quickly.

Mucosal immune responses in the lung during respiratory infection:The organization and regulation of iBALT structure

The local immune defenses of respiratory system play a crucial role in safeguarding against pathogens and eliminating infected cells.In this article,we review the current knowledge regarding the establishment and regulation of local im-mune responses within the lungs,with a particular focus on the formation of inducible bronchus-associated lymphoid tissue(iBALT),which has demonstrated a capacity to mount protective immune responses against several pathogens,including influenza virus,severe acute respiratory syndrome coronavirus(SARS-CoV)/SARS-CoV-2,and Mycobacte-rium tuberculosis(Mtb).Furthermore,we explore the development and regulation of long-term immune memory within the lungs,which may be facilitated by iBALT.This review aims to provide a summary of potential targets within iBALT for pathogen defense and vaccine design.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees

Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.

Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)therapy.Therefore,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy.Here,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor cells.We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell infiltration.Moreover,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo.In order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor recurrence.We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Dynamic detection for computer virus based on immune system

Inspired by biological immune system, a new dynamic detection model for computer virus based on immune system is proposed. The quantitative description of the model is given. The problem of dynamic description for self and nonself in a computer virus immune system is solved, which reduces the size of self set. The new concept of dynamic tolerance, as well as the new mechanisms of gene evolution and gene coding for immature detectors is presented, improving the generating efficiency of mature detectors, reducing the false-negative and false-positive rates. Therefore, the difficult problem, in which the detector training cost is exponentially related to the size of self-set in a traditional computer immune system, is thus overcome. The theory analysis and experimental results show that the proposed model has better time efficiency and detecting ability than the classic model ARTIS.

Memory NK cells： why do they reside in the liver？

Immune memory is the hallmark of adaptive immunity. However, recent studies have shown that natural killer （NK） cells, key components of the innate immune system, also mediate memory responses in mice and humans. Strikingly, memory NK cells were liver-resident in some models, raising the question as to whether the liver is a special organ for the acquisition of NK cell memory. Here, we review the characteristics of N K cell memory by summarizing recent progress and discuss how the liver may generate both the initiation and the recall phase of memory. We propose that the liver may have unique precursors for memory NK cells, which are developmentally distinct from NK cells derived from bone marrow.

Photosynthetic microorganisms coupled photodynamic therapy for enhanced antitumor immune effect

The ideal photodynamic therapy(PDT)should effectively remove the primary tumor,and produce a stronger immune memory effect to inhibit the tumor recurrence and tumor metastasis.However,limited by the hypoxic and immunosuppressive microenvironment,the PDT efficiency is apparently low.Here,Chlorella(Chl.)is exploited to enhance local effect by producing oxygen to reverse hypoxia,and release adjuvants to reverse immunosuppressive microenvironment to enhance abscopal effect afterwards.Results from different animal models indicated that Chl.could enhance local effect and PDT related immune response.Ultimately,Chl.coupled PDT elicited anti-tumor effects toward established primary tumors(inhibition rate:90%)and abscopal tumors(75%),controlled the challenged tumors(100%)and alleviated metastatic tumors(90%).This Chl.coupled PDT strategy can also produce a stronger anti-tumor immune memory effect.Overall,this Chl.coupled PDT strategy generates enhanced local tumor killing,boosts PDT-induced immune responses and promotes anti-tumor immune memory effect,which may be a great progress for realizing systemic effect of PDT.

Epigenetic regulation of macrophages: from homeostasis maintenance to host defense

Macrophages are crucial members of the innate immune response and important regulators.The differentiation and activation of macrophages require the timely regulation of gene expression,which depends on the interaction of a variety of factors,including transcription factors and epigenetic modifications.Epigenetic changes also give macrophages the ability to switch rapidly between cellular programs,indicating the ability of epigenetic mechanisms to affect phenotype plasticity.In this review,we focus on key epigenetic events associated with macrophage fate,highlighting events related to the maintenance of tissue homeostasis,responses to different stimuli and the formation of innate immune memory.Further understanding of the epigenetic regulation of macrophages will be helpful for maintaining tissue integrity,preventing chronic inflammatory diseases and developing therapies to enhance host defense.