Covid-19 vaccine immunogenicity in people living with HIV-1

IntroductionCOVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals’ response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals.MethodsHIV-positive individuals (n = 121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naïve to SARS CoV-2 was used. The participants’ Anti-RBD IgG responses were measured by ELISA at baseline and 3–4 weeks after receiving the first dose of an mRNA vaccine).ResultsEleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between the HIV negative control group (n = 20) and the combined HIV+ group (n = 106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm³. (p < 0.0001). Increasing age was independently associated with decreased immunogenicity.ConclusionHIV-positive individuals with CD4 counts over 250 cells/mm³ have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm³) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose.     

Immunogenicity of two doses of BNT162b2 and mRNA-1273 vaccines for solid cancer patients on treatment with or without a previous SARS-CoV-2 infection

Previous studies on the immunogenicity of SARS-CoV-2 mRNA vaccines showed a reduced seroconversion in cancer patients. The aim of our study is to evaluate the immunogenicity of two doses of mRNA vaccines in solid cancer patients with or without a previous exposure to the virus. This is a single-institution, prospective, nonrandomized study. Patients in active treatment and a control cohort of healthy people received two doses of BNT162b2 (Comirnaty, BioNTech/Pfizer, The United States) or mRNA-1273 (Spikevax, Moderna). Vaccine was administered before starting anticancer therapy or on the first day of the treatment cycle. SARS-CoV-2 antibody levels against S1, RBD (to evaluate vaccine response) and N proteins (to evaluate previous infection) were measured in plasma before the first dose and 30 days after the second one. From January to June 2021, 195 consecutive cancer patients and 20 healthy controls were enrolled. Thirty-one cancer patients had a previous exposure to SARS-CoV-2. Cancer patients previously exposed to the virus had significantly higher median levels of anti-S1 and anti-RBD IgG, compared to healthy controls (P = .0349) and to cancer patients without a previous infection (P < .001). Vaccine type (anti-S1: P < .0001; anti-RBD: P = .0045), comorbidities (anti-S1: P = .0274; anti-RBD: P = .0048) and the use of G-CSF (anti-S1: P = .0151) negatively affected the antibody response. Conversely, previous exposure to SARS-CoV-2 significantly enhanced the response to vaccination (anti-S1: P < .0001; anti-RBD: P = .0026). Vaccine immunogenicity in cancer patients with a previous exposure to SARS-CoV-2 seems comparable to that of healthy subjects. On the other hand, clinical variables of immune frailty negatively affect humoral immune response to vaccination.     

液氮冻存降低成骨细胞免疫原性的实验研究

目的:探讨液氮冷冻(fluid nitrogen cryopreservation)对成骨细胞免疫原性的影响。方法:体外培养成骨细胞,传代鉴定后液氮冻存3个月,复苏。利用流式细胞仪(flow cytometry,FCM),通过间接免疫荧光技术测定冻存前后成骨细胞的免疫原性。同时采用成骨细胞、淋巴细胞混合培养(osteoblasts and lymphocytes mixed culture,OLMC)的方法,测定液氮冷冻对成骨细胞免疫原性的影响。结果:体外培养细胞经鉴定为成骨细胞,液氮冻存3个月后存活率>90%。FCM及OLMC实验结果均表明冻存后成骨细胞的免疫原性显著降低(P<0.01)。结论:低温液氮冷冻是一种理想的降低成骨细胞免疫原性的方法。     

Immunogenicity of branched polyethylene glycol modified interferon alpha

Aim: To assess the immunogenicity of Peginterferon alpha-2?b(Pegberon) and its effect on the efficacy and safety in phase III clinical trial, by comparing it with the control drug Pegasys.

Methods: 770 patients were recruited in total. 509 were treated with Pegberon plus ribavirin and 261 were treated with Pegasys plus ribavirin. After treatment of 12 and 24?weeks, plasma samples were collected from individual patients for detecting the anti-therapeutic antibodies (ATA) and hepatitis C RNA(HCV RNA), to evaluate the production of antibodies and their adverse effect on the efficacy and safety of the treatments. With data obtained from the treatments with Pegberon or Pegasys, gross comparison analysis was performed.

Results: The incidence of treatment-induced neutralizing antibodies (NAb) of Pegberon group (0.7%, 3/454) was significantly lower than Pegasys group (5.0%,12/238)(p?p?=?.010), between baseline NAb positive (36.0%,9/25) and baseline NAb negative patients (76.4%,569/745)(p?p?=?.034). The incidence of potential immunogenicity-related adverse reactions (AR) showed no significant difference between Pegberon (55.6%,283/509) and Pegasys groups (53.6%,140/261)(p?=?.605) and the profiles of these AR were also similar between the two groups.

Conclusion: The incidence of treatment-induced Nab in Pegasys group was significantly higher than the Pegberon group. Baseline ATA, induced ATA and baseline NAb all affected the efficacy. The profiles of potential immunogenicity-related AR were similar between two drug groups, indicating the immunogenicity had no significant adverse effect on safety.     

Predicted MHC peptide binding promiscuity explains MHC class I ‘hotspots’ of antigen presentation defined by mass spectrometry eluted ligand data

Peptides that bind to and are presented by MHC class I and class II molecules collectively make up the immunopeptidome. In the context of vaccine development, an understanding of the immunopeptidome is essential, and much effort has been dedicated to its accurate and cost‐effective identification. Current state‐of‐the‐art methods mainly comprise in silico tools for predicting MHC binding, which is strongly correlated with peptide immunogenicity. However, only a small proportion of the peptides that bind to MHC molecules are, in fact, immunogenic, and substantial work has been dedicated to uncovering additional determinants of peptide immunogenicity. In this context, and in light of recent advancements in mass spectrometry (MS), the existence of immunological hotspots has been given new life, inciting the hypothesis that hotspots are associated with MHC class I peptide immunogenicity. We here introduce a precise terminology for defining these hotspots and carry out a systematic analysis of MS and in silico predicted hotspots. We find that hotspots defined from MS data are largely captured by peptide binding predictions, enabling their replication in silico. This leads us to conclude that hotspots, to a great degree, are simply a result of promiscuous HLA binding, which disproves the hypothesis that the identification of hotspots provides novel information in the context of immunogenic peptide prediction. Furthermore, our analyses demonstrate that the signal of ligand processing, although present in the MS data, has very low predictive power to discriminate between MS and in silico defined hotspots.     

A humanized TCR retaining authentic specificity and affinity conferred potent anti‐tumour cytotoxicity

The affinity of T‐cell receptor (TCR) determines the efficacy of TCR‐based immunotherapy. By using human leucocyte antigen (HLA)‐A*02 transgenic mice, a TCR was generated previously specific for human tumour testis antigen peptide MAGE‐A3_112–120 (KVAELVHFL) HLA‐A*02 complex. We developed an approach to humanize the murine TCR by replacing the mouse framework with sequences of folding optimized human TCR variable domains for retaining binding affinity. The resultant humanized TCR exhibited higher affinity and conferred better anti‐tumour activity than its parent murine MAGE‐A3 TCR (SRm1). In addition, the affinity of humanized TCR was enhanced further to achieve improved T‐cell activation. Our studies demonstrated that the human TCR variable domain frameworks could provide support for complementarity‐determining regions from a murine TCR, and retain the original binding activity. It could be used as a generic approach of TCR humanization.     

Erythropoietin-induced, antibody-mediated pure red cell aplasia

Pure red cell aplasia (PRCA) is a rare haematological condition that is characterized by severe aregenerative anaemia due to an almost complete cessation of red blood cell production. While antibody-mediated PRCA was extremely rare before 1998, the incidence of this disorder increased sharply after 1998 in patients receiving subcutaneous epoetin alfa produced by Ortho-Biotech and marketed outside the USA. The diagnosis of antibody-mediated PRCA relies mostly on the results of bone marrow biopsy or aspirate, which shows an absence of erythroid precursors and/or red cell maturation arrest while counts of white cell and platelet precursors are normal, and on the identification of circulating anti-erythropoietin antibodies. Retrospective analysis of PRCA cases has shown that immunosuppressive therapy can induce a disappearance of anti-erythropoietin antibodies in most patients. Eur J Clin Invest 2005; 35 (Suppl. 3): 95-99.     

Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19

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