Is COVID-19 Still a Threat? An Expert Opinion Review on the Continued Healthcare Burden in Immunocompromised Individuals.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. The emergence of several variants during the pandemic has presented numerous challenges in preventing and managing this disease. The development of vaccines has played a pivotal role in controlling the pandemic, with a significant portion of the global population being vaccinated.

Controlled human infection trials: Legitimacy and conditions of implementation in France.

This round table is the result of an observation. The observation being that controlled human infection clinical trials (also called "infectious challenge" trials or "Controlled Human Infection Models", "CHIM") recommended or even encouraged in the context of vaccine developments in particular, are not carried out in France. However, there are no formal prohibitions within regulations or ethical principles, which point to the prior assessment of risks and benefits for individuals and for society.

Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study.

Background: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.

Methods: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients.

Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome.

Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.

Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study.

Background: Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a).

The fully synthetic glycopeptide MAG-Tn3 therapeutic vaccine induces tumor-specific cytotoxic antibodies in breast cancer patients.

Cancer is one of the main causes of mortality worldwide and a major public health concern. Among various strategies, therapeutic vaccines have been developed to stimulate anti-tumoral immune responses. However, in spite of extensive studies, this approach suffers from a lack of efficacy.

Vaccine Development: From Preclinical Studies to Phase 1/2 Clinical Trials.

Vaccines are biological pharmaceutical products prescribed as prevention of a hypothetical infection. Development of a new vaccine is the result of a long process involving several stages. During all developmental phases, priority is the safety of the new product, which is often used in young infants.

Correction to: A multicenter, randomized controlled comparison of three renutrition strategies for the management of moderate acute malnutrition among children aged from 6 to 24 months (the MALINEA project).

After publication of the original article [1], the authors have notified us of an additional acknowledgement they wish to bring for their paper.

A multicenter, randomized controlled comparison of three renutrition strategies for the management of moderate acute malnutrition among children aged from 6 to 24 months (the MALINEA project).

Background: The aim of this open-label, randomized controlled trial conducted in four African countries (Madagascar, Niger, Central African Republic, and Senegal) is to compare three strategies of renutrition for moderate acute malnutrition (MAM) in children based on modulation of the gut microbiota with enriched flours alone, enriched flours with prebiotics or enriched flours coupled with antibiotic treatment.

Methods: To be included, children aged between 6 months and 2 years are preselected based on mid-upper-arm circumference (MUAC) and are included based on a weight-for-height Z-score (WHZ) between - 3 and - 2 standard deviations (SD). As per current protocols, children receive renutrition treatment for 12 weeks and are assessed weekly to determine improvement.

Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial.

Background: Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy.

Large-scale synthesis and structural analysis of a synthetic glycopeptide dendrimer as an anti-cancer vaccine candidate.

Herein, we report a new process that enables the gram-scale production of a fully synthetic anti-cancer vaccine for human use. This therapeutic vaccine candidate, named MAG-Tn3, is a high-molecular-weight tetrameric glycopeptide encompassing carbohydrate tumor-associated Tn antigen clusters and peptidic CD4 T-cell epitopes. The synthetic process involves (i) the stepwise solid-phase assembly of protected amino acids, including the high value-added Tn building blocks with only 1.

The fully synthetic MAG-Tn3 therapeutic vaccine containing the tetanus toxoid-derived TT830-844 universal epitope provides anti-tumor immunity.

Malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. Of these carbohydrate antigens, the Tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. We designed MAG-Tn3, a fully synthetic vaccine based on three consecutive Tn moieties that are O-linked to a CD4+ T cell epitope, to induce anti-Tn antibody responses that could be helpful for therapeutic vaccination against cancer.

Carbohydrate mimetic peptides augment carbohydrate-reactive immune responses in the absence of immune pathology.

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between "tumor destruction" and "tissue damage", as mono- and disaccharides are also expressed on normal tissue.

Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells.

Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose.

Preclinical studies of carbohydrate mimetic peptide vaccines for breast cancer and melanoma.

Limited immune responses to tumor-associated carbohydrate antigens (TACA) are due in part to their being self-antigens. Immunization with xenoantigens of TACA provides an approach to break tolerance and augment responses to TACA. Carbohydrate mimetic peptides (CMPs) as xenoantigens can induce serum antibodies that target shared carbohydrate residues on differing carbohydrate structures.

Chondroitin sulfate glycosaminoglycans as major P-selectin ligands on metastatic breast cancer cell lines.

The metastatic breast cancer cell line, 4T1, abundantly expresses the oligosaccharide sialylated Lewis x (sLe(x)). SLe(x) oligosaccharide on tumor cells can be recognized by E- and P-selectin, contributing to tumor metastatic process. We observed that both selectins reacted with this cell line.

Evaluating strategies to enhance the anti-tumor immune response to a carbohydrate mimetic peptide vaccine.

Carbohydrate mimetic peptides of tumor associated carbohydrate antigens (TACA) are T-cell-dependent antigens and, therefore, immunization with these surrogates is predicted to overcome the low immunogenicity of carbohydrate antigens. Consistent with this hypothesis, we show that among the potential immune cells involved, peptide immunization led to an increase in T-cell populations. While peptide mimetics may also function as TLR binding ligands, we did not observe evidence of involvement of NK cells.

1H-NMR metabolic markers of malignancy correlate with spontaneous metastases in a murine mammary tumor model.

End-products of glycolysis as well as phospholipid precursors and catabolites have been suggested as metabolic indicators of tumor progression. To test the hypothesis that increased levels of such indicators can distinguish metastatic phenotypes, we determined a limited cellular 1H-NMR metabolic profile of subpopulations of murine mammary 4T1 cells that differ in their metastatic potential. Subpopulations with differing metastatic phenotypes were identified by sorting for the expression of the cell surface adhesion oligosaccharide sialylated Lewis x (sLeX).

Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer.

Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly into the blood. We investigated the relative role of sLe(x) oligosaccharide in the dissemination of breast carcinoma, employing a spontaneous murine metastasis model.

Reduction of spontaneous metastases through induction of carbohydrate cross-reactive apoptotic antibodies.

The selective targeting of tumor-associated carbohydrate Ags by the induction of serum Abs that trigger apoptosis of tumor cells as a means to reduce circulating tumor cells and micrometastases would be an advantage in cancer vaccine development. Some plant lectins like Griffonia simplicifolia lectin I and wheat germ agglutinin mediate the apoptosis of tumor cells. We investigated the possibility of using these lectins as templates to select peptide mimotopes of tumor-associated carbohydrate Ags as immunogens to generate cross-reactive Abs capable of mediating apoptosis of tumor cells.

A mimic of tumor rejection antigen-associated carbohydrates mediates an antitumor cellular response.

Tumor-associated carbohydrate antigens are typically perceived as inadequate targets for generating tumor-specific cellular responses. Lectin profile reactivity and crystallographic studies demonstrate that MHC class I molecules can present to the immune system posttranslationally modified cytosolic peptides carrying O-beta-linked N-acetylglucosamine (GlcNAc). Here we report that a peptide surrogate of GlcNAc can facilitate an in vivo tumor-specific cellular response to established Meth A tumors that display native O-GlcNAc glycoproteins on the tumor cell surface.