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Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptorbinding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross-neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMS:RBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.
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Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need. Receptor-binding domain (RBD) is a key target of neutralizing antibodies (Abs) but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists, including those activating STING, TLR3, TLR4 and TLR9, alone or formulated with aluminum hydroxide (AH), and benchmarked them to AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that the AH and CpG adjuvant formulation (AH:CpG) demonstrated the highest enhancement of anti-RBD neutralizing Ab titers in both age groups ([~]80-fold over AH), and protected aged mice from the SARS-CoV-2 challenge. Notably, AH:CpG-adjuvanted RBD vaccine elicited neutralizing Abs against both wild-type SARS-CoV-2 and B.1.351 variant at serum concentrations comparable to those induced by the authorized mRNA BNT162b2 vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and synergistically enhanced cytokine and chemokine production in human young adult and elderly mononuclear cells. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups. One Sentence SummaryAlum and CpG enhance SARS-CoV-2 RBD protective immunity, variant neutralization in aged mice and Th1-polarizing cytokine production by human elder leukocytes.
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This paper analyzed the clinical data of 17 patients with inhalation dimethyl sulfate poisoning in Changzhou Third People's Hospital, in order to understand the clinical characteristics, treatment and prognosis of patients with inhalation dimethyl sulfate poisoning, and guide clinicians to make effective measures in time. Dimethyl sulfate poisoning progresses rapidly and dangerously. The prognosis is usually better if the patients are separated from the toxic environment as soon as possible, given glucocorticoids in early and short-term, closely observed respiratory tract injury, and treated with endotracheal intubation and invasive mechanical ventilation when necessary.
Assuntos
Humanos , Respiração Artificial , Ésteres do Ácido SulfúricoRESUMO
Published online: March 4, 2016 (DOI: 10.4238/gmr.15016752). Corrected after publication: June 3, 2016 (DOI: 10.4238/gmr.150267521). The information of authors' affiliations is as follows: Y. L. Chai(1,2), J.Z. Xu(1), Y.L. Zhang(1) and G.T. Sheng(2). (1)Department of Cardiovascular Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China. (2)No.1 Department of Cardiovascular Medicine, People's Hospital of Jiangxi Province, Nanchang, Jiangxi, China.
