Clinical features of influenza with plastic bronchitis in children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of influenza with plastic bronchitis (PB) in children, and to improve the awareness of the diagnosis and treatment of PB caused by influenza virus.@*METHODS@#A retrospective analysis was performed for the clinical data of 70 children with lower respiratory influenza virus infection from October 2018 to October 2019. According to the presence or absence of PB, they were divided into an influenza+PB group with 12 children and a non-PB influenza group with 58 children. Related clinical data were collected for the retrospective analysis, including general information, clinical manifestations, laboratory examination, imaging findings, treatment, and prognosis.@*RESULTS@#In the influenza+PB group, most children experienced disease onset at the age of 1-5 years, with the peak months of January, February, July, and September. Major clinical manifestations in the influenza+PB group included fever, cough, and shortness of breath. The influenza+PB group had significantly higher incidence rates of shortness of breath and allergic diseases such as asthma than the non-PB influenza group (P<0.05). Of the 12 children in the influenza+PB group, 7(58%) had influenza A virus infection and 5 (42%) had influenza B virus infection, among whom 1 had nephrotic syndrome. For the children in the influenza+PB group, major imaging findings included pulmonary consolidation with atelectasis, high-density infiltration, pleural effusion, and mediastinal emphysema. Compared with the non-PB influenza group, the influenza+PB group had a significantly higher proportion of children who were admitted to the pediatric intensive care unit (P<0.05). Bronchoscopic lavage was performed within 1 week after admission, and all children were improved and discharged after anti-infective therapy and symptomatic/supportive treatment.@*CONCLUSIONS@#Influenza with PB tends to have acute onset and rapid progression, and it is important to perform bronchoscopy as early as possible. The possibility of PB should be considered when the presence of shortness of breath, allergic diseases such as asthma or nephrotic syndrome in children with influenza.

A novel fully human anti-CD47 antibody as a potential therapy for human neoplasms with good safety.

Strategies for targeting CD47 are becoming a hot spot of cancer immunotherapy. However the ubiquitous expression of CD47, especially on the RBC, makes the targeted therapy facing safety risk issues. So, how to balance the safety and efficacy during CD47 inhibition is currently a major question. We had reported an anti-CD47 antibody ZF1 with potent anti-tumor effect. In this study, we further developed and assessed a novel fully human anti-CD47 antibody, AMMS4-G4, derived from ZF1 using affinity maturation. AMMS4-G4 exhibited equivalent anticancer effects with Hu5F9-G4, a humanized anti-CD47 antibody in clinical trial, on the potential of inducing significant phagocytosis of tumor cells in vitro and prolonging the survival of leukemia xenografted mice. Additionally, AMMS4-G4 significantly inhibited the growth of grafted solid tumors by enhancing macrophage infiltration and modestly enhanced the anti-tumor activity of opsonizing antibody and antiangiogenic therapy. In cynomolgus monkeys, AMMS4-G4 was safely administered, was well tolerated at doses of 30 and 60 mg/kg, and did not produce serious adverse events, except for the reversible anemia, which was observed after 3 days and started to recover from 9 days later. Remarkably, it was proved by in vitro assay that Hu5F9-G4 induced RBC hemagglutination which wasn't observed in AMMS4-G4. On the whole, AMMS4-G4 was demonstrated to be a promising candidate with great potential and safe profile for cancer immunotherapy.

Strikingly reduced amyloid burden and improved behavioral performance in Alzheimer's disease mice immunized with recombinant chimeric vaccines by hexavalent foldable Aß1₋15 fused to toxin-derived carrier proteins.

Targeting on the amyloid-ß (Aß) is a promising immunotherapeutic strategy for Alzheimer's disease (AD). However, Aß(1-15) sequence alone induces low antibody response and poor protection against AD. We describe here the immunological characterization and protective efficacy of several recombinant chimeric vaccines with hexavalent foldable Aß(1-15) (6Aß15) fused to PADRE or toxin-derived carrier proteins. Immunization with these chimeric antigens generated robust Th2 immune responses with high anti-Aß42 antibody titers in different mice, which recognized neurotoxic Aß42 oligomers, but did not stimulate Aß42-specific T cell responses. These 6Aß15 chimeric vaccines markedly reduced Aß pathology and prevented development of behavioral deficits in immunized older AD mice. Importantly, toxin-derived carrier proteins as molecular adjuvants of chimeric vaccines could substantially boost immune responses and overcome Aß- and old age-associated hypo-responsiveness, and elicit long-term Aß-specific antibody response, which in turn inhibited Aß-mediated pathology and improved acquisition and retention of spatial memory in immunized AD mice. These data indicate that toxin fragments as molecular adjuvants are promising new tools for the rational design and development of prototype chimeric vaccines for AD and this type of chimeric vaccine design has the added advantage of overcoming hypo-responsiveness in elderly AD patients with pre-existing memory Th cells from tetanus toxin.

Effective DNA epitope chimeric vaccines for Alzheimer's disease using a toxin-derived carrier protein as a molecular adjuvant.

Active amyloid-beta (Aß) immunotherapy is under investigation to prevent or treat Alzheimer disease (AD). We describe here the immunological characterization and protective effect of DNA epitope chimeric vaccines using 6 copies of Aß1-15 fused with PADRE or toxin-derived carriers. These naked 6Aß15-T-Hc chimeric DNA vaccines were demonstrated to induce robust anti-Aß antibodies that could recognize Aß oligomers and inhibit Aß oligomer-mediated neurotoxicity, result in the reduction of cerebral Aß load and Aß oligomers, and improve cognitive function in AD mice, but did not stimulate Aß-specific T cell responses. Notably, toxin-derived carriers as molecular adjuvants were able to substantially promote immune responses, overcome Aß-associated hypo-responsiveness, and elicit long-term Aß-specific antibody response in 6Aß15-T-Hc-immunized AD mice. These findings suggest that our 6Aß15-T-Hc DNA chimeric vaccines can be used as a safe and effective strategy for AD immunotherapy, and toxin-derived carrier proteins are effective molecular adjuvants of DNA epitope vaccines for Alzheimer's disease.