Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

Background Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration > 10 BAU/mL and a previous SARS-CoV-2 infection as N IgG > 14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wildtype (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution

Chronische orale graft-versus-hostziekte

Graft-versus-hostziekte (graft versus host disease; gvhd) is een veelvoorkomende complicatie na allogene stamceltransplantatie. Vooral chronische gvhd (cgvhd) manifesteert zich vaak (peri)oraal. Zo kunnen bij cgvhd de orale slijmvliezen pijnlijk zijn, smaakveranderingen optreden en de speekselklieren zijn aangedaan. Soms treden er tevens invaliderende scleroserende veranderingen in het hoofd-halsgebied op. Patiënten hebben dan een beperkte mondopening waardoor, in combinatie met de pijnlijke slijmvliezen, een goede mondhygiëne en tandheelkundige behandeling worden bemoeilijkt. De immunologische afweer is verminderd ten gevolge van de ziekte zelf en interventies gericht op preventie en behandeling van cgvhd. Dit vergroot het risico op infecties, vooral door schimmels en virussen. Bij hyposialie en/of een veranderde samenstelling van het speeksel kan een snel voortschrijdende vorm van cariës optreden. Al deze mondproblemen bemoeilijken een adequate intake en verminderen de kwaliteit van leven. Tandheelkundige professionals kunnen een belangrijke bijdrage leveren aan de preventie van en de ondersteunende zorg bij deze complicaties. Dit wordt aan de hand van een casus nader toegelicht

Chronic oral graft-versus-host disease: induction and maintenance therapy with photobiomodulation therapy

Abstract: This study presents follow-up of a prior study of patients with chronic symptomatic oral chronic graft-versus-host-disease (cGVHD) managed with photobiomodulation therapy (PBM therapy for 1 month. Here, we report long-term follow-up of a series of patients where PBM therapy in patients with oral cGVHD for maintenance follows the initial period of PBM therapy for continuing management. Patients and methods: We report continuing follow-up of 7 cases of oral cGVHD that were treated with PBM therapy. PBM therapy was continued in these patients with the goal of determining the best management schedule of PBM to maintain or improve control of each patient’s symptoms and signs of oral cGVHD. Results: Oral sensitivity and mucosal changes of cGVHD were controlled with a continuing schedule of PBM therapy of up to 6–8-week treatment intervals in patients with continuing GVHD. These findings suggest that PBM therapy represents an additional approach for continuing management of oral cGVHD and that the frequency of treatment should be individualized for each patient to provide best control of oral findings. In one case weekly PBM treatment was continued, while in others, management on a monthly or bimonthly basis was associated with control of the oral condition. PBM may be individualized and provided based upon best control of the symptoms and signs of oral GVHD

The role of mutation accumulation in HIV progression

The onset of AIDS is characterized by the collapse of the immune system after a prolonged asymptomatic period. The mechanistic basis of this disease progression has remained obscure, hindering the development of effective therapies. Here I present a mechanism that underlies the deterioration of the immune system during HIV infection. The elevated turnover of lymphocytes throughout the asymptomatic period is postulated to result in the accumulation of deleterious mutations, which impairs immunological function, replicative ability and viability of lymphocytes. This mutational meltdown is proposed to occur throughout the hierarchy of lymphocyte progenitors, resulting in the deterioration of lymphocyte regeneration and an ensuing rise in viral loads. A mathematical model is used to illustrate this mechanism of progressive immunological deterioration. Mutation accumulation may explain not only the decline in CD4(+)T cells, but also the functional deterioration of CD4(+)T cells, CD8(+)T cells and B cells, and the exhaustion of lymphocyte regeneration

[Oral chronic graft versus host disease, what is it and how is it treated?]

Allogeneic stem cell transplantation can cause chronic graft versus host disease (cGVHD). A number of patients manifest cGVHD in and around the mouth. It can present itself as clinically as mucosal lesions and/or salivary gland dysfunction and/or sclerotic changes. Cheeks and tongue are most commonly affected, but the palate, gingiva and lips can also be impacted. Oral cGVHD is associated with mucosal sensitivity, pain, (severe) oral dryness, altered taste, restricted mouth opening and difficulty swallowing, all of which may contribute to a significant decrease of the patient's quality of life. Patients also run an increased risk of developing squamous cell carcinoma of the oral mucosa. The diagnosis of cGVHD is almost always based on the patient's medical history and clinical picture. Treatment of symptoms is based on the patient's problem(s). Dental professionals can provide patients with supportive preventive care aimed at reducing symptoms and preventing further deterioration of oral health

Establishment of the CD4+T cell pool in healthy and untreated HIV-1 infected children.

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Tumor Specific Glycosylated CD43 Is a Novel and Highly Specific Target for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Proteomic

An antibody derived from a cured AML patient to identify a unique epitope on CD43 (CD43s) as a novel target for acute myeloid leukemia and myelodysplastic syndrome

Proteomic