Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor-binding domain (RBD).

Second-generation COVID-19 vaccines with improved immunogenicity (e.g., breadth, duration) and availability (e.g., lower costs, refrigerator stable) are needed to enhance global coverage. In this work, we formulated a clinical-stage SARS-CoV-2 receptor-binding domain (RBD) virus-like particle (VLP) vaccine candidate (IVX-411) with widely available adjuvants. Specifically, we assessed the in vitro storage stability and in vivo mouse immunogenicity of IVX-411 formulated with aluminum-salt adjuvants (Alhydrogel™, AH and Adjuphos™, AP), without or with the TLR-9 agonist CpG-1018™ (CpG), and compared these profiles to IVX-411 adjuvanted with an oil-in-water nano-emulsion (AddaVax™, AV). Although IVX-411 bound both AH and AP, lower binding strength of antigen to AP was observed by Langmuir binding isotherms. Interestingly, AH- and AP-adsorbed IVX-411 had similar storage stability profiles as measured by antigen-binding assays (competitive ELISAs), but the latter displayed higher pseudovirus neutralizing titers (pNT) in mice, at levels comparable to titers elicited by AV-adjuvanted IVX-411. CpG addition to alum (AP or AH) resulted in a marginal trend of improved pNTs in stressed samples only, yet did not impact the storage stability profiles of IVX-411. In contrast, previous work with AH-formulations of a monomeric RBD antigen showed greatly improved immunogenicity and decreased stability upon CpG addition to alum. At elevated temperatures (25, 37°C), IVX-411 formulated with AH or AP displayed decreased in vitro stability compared to AV-formulated IVX-411and this rank-ordering correlated with in vivo performance (mouse pNT values). This case study highlights the importance of characterizing antigen-adjuvant interactions to develop low cost, aluminum-salt adjuvanted recombinant subunit vaccine candidates.

Radiological and clinical assessment of long-term brain tumour survivors after radiotherapy.

BACKGROUND AND PURPOSE: Late adverse effects of therapeutic brain radiotherapy (RT) may develop after long latency periods and our objective was to assess long-term brain tumour survivors following RT to large partial brain volumes. MATERIALS AND METHODS: Assessment of MRI, SOMA/LENT score, quality of life and neuroendocrine function was performed in 33 adult brain tumour patients 6-25 years following RT. Fraction dose was 1.8 Gy to a median total dose of 54 Gy (range: 45.0-59.4 Gy). Ten patients had been given two opposing portals including one whole hemisphere, while 23 patients had in addition received an ipsilateral field. In 25 patients the hypothalamic and pituitary area had been included in the RT field. Results were compared within the study group and towards the general population matched for age and gender. RESULTS: All patients had white matter changes with increased signal intensity on T2 and FLAIR images. Discrete lesions (grade 1), beginning confluence of lesions (grade 2), and large confluent areas (grade 3) were present in 8, 8 and 17 patients, respectively. Patients treated with intra-arterial chemotherapy and patients at higher age at follow-up had significantly more grade 3 changes. Atrophy, lacunar lesions and contrast enhancement was found in 17, 18 and 23 patients, respectively. Significantly worse clinical status and quality of life was found in patients with white matter changes grade 3 or atrophy. Patients given full-dose RT to less volume did not have significantly less toxicity. Two cases of meningioma were found at 16 and 22 years after RT. Nineteen neuroendocrine abnormalities were observed in 16/25 patients. CONCLUSIONS: External radiotherapy to the brain at a standard fractionation regime will cause varying degrees of late neurotoxicity and/or neuroendocrine disturbances in most patients. Life-long follow-up is recommended.

Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses.

PURPOSE: To determine preoperative parameters that predict the histology of specimens obtained by retroperitoneal lymph node dissection (RPLND) in patients with nonseminomatous germ cell cancer (NSGCT) whose residual mass was