New Novavax vaccine OK'd; studies size it up against mRNA.

Limited data and lack of head-to-head studies make comparisons between shots tricky.

Cancer immunotherapies: advances and bottlenecks.

Immunotherapy has ushered in a new era in cancer treatment, and cancer immunotherapy continues to be rejuvenated. The clinical goal of cancer immunotherapy is to prime host immune system to provide passive or active immunity against malignant tumors. Tumor infiltrating leukocytes (TILs) play an immunomodulatory role in tumor microenvironment (TME) which is closely related to immune escape of tumor cells, thus influence tumor progress. Several cancer immunotherapies, include immune checkpoint inhibitors (ICIs), cancer vaccine, adoptive cell transfer (ACT), have shown great efficacy and promise. In this review, we will summarize the recent research advances in tumor immunotherapy, including the molecular mechanisms and clinical effects as well as limitations of immunotherapy.

Classification related to immunogenic cell death predicts prognosis, immune microenvironment characteristics, and response to immunotherapy in lower-grade gliomas.

Background: Immunogenic cell death (ICD) is a form of cell death that elicits immune responses against the antigens found in dead or dying tumor cells. Growing evidence implies that ICD plays a significant role in triggering antitumor immunity. The prognosis for glioma remains poor despite many biomarkers being reported, and identifying ICD-related biomarkers is imminent for better-personalized management in patients with lower-grade glioma (LGG). Materials and methods: We identified ICD-related differentially expressed genes (DEGs) by comparing gene expression profiles obtained across Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) cohorts. On the foundation of ICD-related DEGs, two ICD-related clusters were identified through consensus clustering. Then, survival analysis, functional enrichment analysis, somatic mutation analysis, and immune characteristics analysis were performed in the two ICD-related subtypes. Additionally, we developed and validated a risk assessment signature for LGG patients. Finally, we selected one gene (EIF2AK3) from the above risk model for experimental validation. Results: 32 ICD-related DEGs were screened, dividing the LGG samples from the TCGA database into two distinct subtypes. The ICD-high subgroup showed worse overall survival (OS), greater immune infiltration, more active immune response process, and higher expression levels of HLA genes than the ICD-low subgroup. Additionally, nine ICD-related DEGs were identified to build the prognostic signature, which was highly correlated with the tumor-immune microenvironment and could unambiguously be taken as an independent prognostic factor and further verified in an external dataset. The experimental results indicated that EIF2AK3 expression was higher in tumors than paracancerous tissues, and high-expression EIF2AK3 was enriched in WHO III and IV gliomas by qPCR and IHC, and Knockdown of EIF2AK3 suppressed cell viability and mobility in glioma cells. Conclusion: We established novel ICD-related subtypes and risk signature for LGG, which may be beneficial to improving clinical outcome prediction and guiding individualized immunotherapy.

Expression characteristics of non-virion protein of Hirame novirhabdovirus and its transfection induced response in hirame natural embryo cells.

The non-virion (NV) protein is the signature of genus Novirhabdovirus, which has been of considerable concern due to its potential role in viral pathogenicity. However, its expression characteristics and induced immune response remain limited. In the present work, it was demonstrated that Hirame novirhabdovirus (HIRRV) NV protein was only detected in the viral infected hirame natural embryo (HINAE) cells, but absent in the purified virions. Results showed that the transcription of NV gene could be stably detected in HIRRV-infected HINAE cells at 12 h post infection (hpi) and then reached the peak at 72 hpi. A similar expression trend of NV gene was also found in HIRRV-infected flounders. Subcellular localization analysis further exhibited that HIRRV-NV protein was predominantly localized in the cytoplasm. To elucidate the biological function of HIRRV-NV protein, NV eukaryotic plasmid was transfected into HINAE cells for RNA-seq. Compared to empty plasmid group, some key genes in RLR signaling pathway were significantly downregulated in NV-overexpressed HINAE cells, indicating that RLR signaling pathway was inhibited by HIRRV-NV protein. The interferon-associated genes were also significantly suppressed upon transfection of NV gene. This research would improve our understanding of expression characteristics and biological function of NV protein during HIRRV infection process.

Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers.

Breastfeeding is associated with long-term wellbeing including low risks of infectious diseases and non-communicable diseases such as asthma, cancer, autoimmune diseases and obesity during childhood. In recent years, important advances have been made in understanding the human breast milk (HBM) composition. Breast milk components such as, non-immune and immune cells and bioactive molecules, namely, cytokines/chemokines, lipids, hormones, and enzymes reportedly play many roles in breastfed newborns and in mothers, by diseases protection and shaping the immune system of the newborn. Bioactive components in HBM are also involved in tolerance and appropriate inflammatory response of breastfed infants if necessary. This review summarizes the current literature on the relationship between mother and her infant through breast milk with regard to disease protection. We will shed some light on the mechanisms underlying the roles of breast milk components in the maintenance of health of both child and mother.

Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNe-short- And long-term Immune reSponSe evAluatioN in health Care workErs.

OBJECTIVE: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. METHODS: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription-polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. RESULTS: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. CONCLUSION: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.

Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant N-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein.

Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.

Chitosan and alginate salt as biomaterials are potential natural adjuvants for killed cholera vaccine.

Chitosan and alginate salts are natural biopolymers that have gained recent attention in the biomedical sectors. Their properties allow them to become potential candidates as safe, cheap, and effective vaccine adjuvants. The present study aimed to enhance the immunogenic response of a current injectable killed cholera vaccine (KCV) using chitosan and alginate salt as natural adjuvants against alum. We tested KCV adjuvanted with alum, chitosan, and sodium alginate in mice. Mice were immunized intraperitoneally with KCV adjuvanted with alum, chitosan, or alginate salt and compared with a control unadjuvanted immunized group. Humoral, cellular, and functional immune responses were evaluated in all groups. The addition of adjuvants, particularly natural adjuvants, to KCV significantly improved the immune response as demonstrated by specific antibody increase, strong proliferation effects, and high protection rate against different challenge doses of cholera strains. Our findings demonstrate that chitosan and alginate salt are superior adjuvants for boosting the KCV immune response and highlights the requirement for further vaccine development.

Immune function of zhenqi fuzheng capsule on volleyball players after high intensity training / Função imunitária da cápsula zhenqi fuzheng em jogadores de voleibol após treinamento de alta intensidade / Efecto de la cápsula zhenqi fuzheng sobre la función inmune de los jugadores de voleibol después del entrenamiento de alta intensidad

ABSTRACT At present, many studies have proved that proper exercise can promote the immune function of human body to a certain extent, but athletes need a lot of high-intensity sports training, and their immune function declines instead of improving. In order to control the decline of immune function of athletes after high-intensity training, this study propose the Zhenqi Fuzheng capsule to achieve this goal. Through experimental comparison, the parameters such as white blood cell content, immunoglobulin number, T lymphocyte, human hemoglobin content and exercise exhaustion time were detected after high-intensity training. The results showed that compared with the control group taking Zhenqi Fuzheng, the weight of those who had taken qifuzhengs capsule did not change, and the content of white blood cells, immunoglobulin, hemoglobin content and exercise time increased to a certain extent. The results showed that Zhenqi Fuzheng could inhibit the decrease of body immune function after high-intensity exercise, then accelerate the recovery of human immune function. This study is expected to enhance the immunity of sports athletes, and reduce athletes' pain after high-intensity training.

RESUMO Atualmente, muitos estudos prova que exercícios adequados podem promover a função imunológica do corpo humano em certa medida, mas os atletas precisam de muito treinamento esportivo de alta intensidade, e sua função imunológica diminui em vez de melhorar. A fim de controlar o declínio da função imunológica dos atletas após treinamento de alta intensidade, este estudo propôs a administração da cápsula Zhenqi Fuzheng para alcançar esse objetivo. Através de comparação experimental, foram detectados parâmetros como o teor de glóbulos brancos, imunoglobulina, linfócitos T, hemoglobina humana e tempo de exaustão do exercício após treinamento de alta intensidade. Os resultados mostraram que, em comparação com o grupo controle que tomou a cápsula Zhenqi Fuzheng, o peso daqueles que tinham tomado a cápsula de qifuzheng não se alterou, e o teor de glóbulos brancos, imunoglobulina, hemoglobina e o tempo de exercício aumentaram em certa medida. Os resultados mostraram que a cápsula Zhenqi Fuzheng poderia inibir a diminuição da função imunológica corporal após exercícios de alta intensidade, e acelerar a recuperação da função imunológica humana. Espera-se que este estudo possa aumentar a imunidade dos atletas e reduzir a dor dos atletas após treinamento alta intensidade para fornecer uma certa referência.

RESUMEN Actualmente, muchos estudios prueban que ejercicios adecuados pueden promover la función inmunológica del cuerpo humano en cierta medida, pero los atletas precisan mucho entrenamiento deportivo de alta intensidad, y su función inmunológica disminuye en vez de mejorar. A fin de controlar la declinación de la función inmunológica de los atletas después del entrenamiento de alta intensidad, este estudio propuso la administración de la cápsula Zhenqi Fuzheng para alcanzar ese objetivo. Por medio de comparación experimental, fueron detectados parámetros como el tenor de glóbulos blancos, inmunoglobulina, linfocitos T, hemoglobina humana y tiempo de agotamiento del ejercicio después de entrenamiento de alta intensidad. Los resultados mostraron que, en comparación con el grupo control que tomó la cápsula Zhenqi Fuzheng, el peso de aquellos que habían tomado la cápsula de qifuzheng no se alteró, y el tenor de glóbulos blancos, inmunoglobulina, hemoglobina y el tiempo de ejercicio aumentaron en cierta medida. Los resultados mostraron que la cápsula Zhenqi Fuzheng podría inhibir la disminución de la función inmunológica corporal después de ejercicios de alta intensidad, y acelerar la recuperación de la función inmunológica humana. Se espera que este estudio pueda aumentar la inmunidad de los atletas y reducir el dolor después de entrenamiento de alta intensidad para proveer una cierta referencia.

Effects of maternal immune activation in porcine transcript isoforms of neuropeptide and receptor genes.

The prolonged effects of maternal immune activation in response stressors during gestation on the offspring's molecular pathways after birth are beginning to be understood. An association between maternal immune activation and neurodevelopmental and behavior disorders such as autism and schizophrenia spectrum disorders has been detected in long-term gene dysregulation. The incidence of alternative splicing among neuropeptides and neuropeptide receptor genes, critical cell-cell signaling molecules, associated with behavior may compromise the replicability of reported maternal immune activation effects at the gene level. This study aims to advance the understanding of the effect of maternal immune activation on transcript isoforms of the neuropeptide system (including neuropeptide, receptor and connecting pathway genes) underlying behavior disorders later in life. Recognizing the wide range of bioactive peptides and functional receptors stemming from alternative splicing, we studied the effects of maternal immune activation at the transcript isoform level on the hippocampus and amygdala of three-week-old pigs exposed to maternal immune activation due to viral infection during gestation. In the hippocampus and amygdala, 29 and 9 transcript isoforms, respectively, had maternal immune activation effects (P-value < 0.01). We demonstrated that the study of the effect of maternal immune activation on neuropeptide systems at the isoform level is necessary to expose opposite effects among transcript isoforms from the same gene. Genes were maternal immune activation effects have also been associated with neurodevelopmental and behavior disorders. The characterization of maternal immune activation effects at the transcript isoform level advances the understanding of neurodevelopmental disorders and identifies precise therapeutic targets.

Immune activation and chronic inflammation: Is there an additional effect of HIV in a geriatric population?

ABSTRACT: HIV infection has become a chronic disease, with a lower mortality, but a consequent increase in age-related noninfectious comorbidities. Metabolic disorders have been linked to the effect of cART as well to the effects of immune activation and chronic inflammation. Whereas it is known that aging is intrinsically associated with hyperinflammation and immune system deterioration, the relative impact of chronic HIV infection on such inflammatory and immune activation has not yet been studied focusing on an elderly HIV-infected population.The objectives of the study were to assess 29 blood markers of immune activation and inflammation using an ultrasensitive technique, in HIV-infected patients aged ≥75 years with no or 1 comorbidity (among hypertension, renal disease, neoplasia, diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and osteoporosis), in comparison with age-adjusted HIV-uninfected individuals to identify whether biomarkers were associated with comorbidities. Wilcoxon nonparametric tests were used to compare the levels of each marker between control and HIV groups; logistic regression to identify biomarkers associated to comorbidity in the HIV group and principal component analysis (PCA) to determine clusters associated with a group or a specific comorbidity.A total of 111 HIV-infected subjects were included from the Dat'AIDS cohort and compared to 63 HIV-uninfected controls. In the HIV-infected group, 4 biomarkers were associated with the risk of developing a comorbidity: monocyte chemoattractant protein-1 (MCP-1), neurofilament light chain (NF-L), neopterin, and soluble CD14. Six biomarkers (interleukin [IL]-1B, IL-7, IL-18, neopterin, sCD14, and fatty acid-binding protein) were significantly higher in the HIV-infected group compared to the control group, 11 biomarkers (myeloperoxydase, interleukin-1 receptor antagonist, tumor necrosis factor receptor 1, interferon-gamma, MCP-1, tumor necrosis factor receptor 2, IL-22, ultra sensitivity C-reactive protein, fibrinogen, IL-6, and NF-L) were lower. Despite those differences, PCA to determine clusters associated with a group or a specific comorbidity did not reveal clustering nor between healthy control and HIV-infected patients neither between the presence of comorbidity within HIV-infected group.In this highly selected geriatric HIV population, HIV infection does not seem to have an additional impact on age-related inflammation and immune disorder. Close monitoring could have led to optimize prevention and treatment of comorbidities, and have limited both immune activation and inflammation in the aging HIV population.

The scientific and ethical feasibility of immunity passports.

There is much debate about the use of immunity passports in the response to the COVID-19 pandemic. Some have argued that immunity passports are unethical and impractical, pointing to uncertainties relating to COVID-19 immunity, issues with testing, perverse incentives, doubtful economic benefits, privacy concerns, and the risk of discriminatory effects. We first review the scientific feasibility of immunity passports. Considerable hurdles remain, but increasing understanding of the neutralising antibody response to COVID-19 might make identifying members of the community at low risk of contracting and transmitting COVID-19 possible. We respond to the ethical arguments against immunity passports and give the positive ethical arguments. First, a strong presumption should be in favour of preserving people's free movement if at all feasible. Second, failing to recognise the reduced infection threat immune individuals pose risks punishing people for low-risk behaviour. Finally, further individual and social benefits are likely to accrue from allowing people to engage in free movement. Challenges relating to the implementation of immunity passports ought to be met with targeted solutions so as to maximise their benefit.