BackgroundCancer vaccines are a promising strategy for cancer immunotherapy. Cancer vaccines elicits a specific cytotoxic immune response to tumor antigens. However, the efficacy of traditional peptide-based cancer vaccines is limited due to the inefficient delivery of antigens and adjuvants to dendritic cells (DCs). Therefore, it is necessary to develop a novel rationally designed cancer vaccine to maximize its desired effects.MethodsA Self-assembling Vehicle-free Multi-component Antitumor nanoVaccine (SVMAV) was constructed by using an unsaturated fatty acid docosahexaenoic acid (DHA)-conjugated antigen and R848 (a Toll-like receptor 7/8 agonist) to encapsulate stattic (a signal transducer and activator of transcription 3 inhibitor). The characteristics of SVMAV were investigated. The ability of SVMAV to promote DC functions was examined by in vitro analysis. The antitumor effects of SVMAV and its combination with antiprogrammed cell death protein 1 antibody (aPD-1) were also investigated in vivo. The potential application of SVMAV for neoantigen-targeted, personalized cancer vaccines was examined in an orthotopic hepatocellular carcinoma model.ResultsThe obtained SVMAV efficiently migrated into lymph nodes and primed CD8+ T cells for exert neoantigen-specific killing by promoting the antigen uptake by DCs, stimulating DC maturation, and enhancing antigen cross-presentation, due to the simultaneous delivery of the antigen, R848 and stattic. SVMAV could not only yield a robust antitumor effect for primary melanoma allografts, but also exert a protective effect for lung metastases. Moreover, combination treatment of SVMAV and aPD-1 exerted synergistic antitumor activity and extended the survival duration of melanoma-bearing mice. Notably, a cell line-specific neoantigen-based SVMAV was designed according to predicted neoantigens for Hepa1-6 cells to examine the potential application of SVMAV for personalized cancer vaccine. Encouragingly, neoantigen-specific SVMAV achieved stronger antitumor activity than aPD-1 in an orthotopic hepatocellular cancer model established with Hepa1-6 cells.ConclusionsIn summary, this study offers an efficient codelivery platform for neoantigens and immunoregulatory compounds to enhance immune responses during cancer immune therapy.

To the Editor, Aplastic anemia (AA) is an auto-activated T cell-mediated bone marrow failure, characterized by pancytopenia and hypocellular marrow. 1 With the worldwide spread of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, patients with AA are at high risk for infection due to disease-related neutropenia and enduring immunosuppressive therapy (IST). 2 Furthermore, AA patients often do not receive the SARS-CoV-2 vaccination due to an ineffective protective specific antibody response to viral antigens and potential immune system activation that may worsen underlying marrow failure.Prior studies have evaluated the clinical manifestation of SARS-CoV-2 infection in severe or very severe AA (SAA/VSAA) patients through case reports or case series, 3-8 but the severity and long-term prognosis of SARS-CoV-2 infection in AA is still not clear.To better explore whether patients with AA experienced more severe symptoms of infection or demonstrated higher relapse rate after infection, we prospectively collected 175 AA patients enrolled in National Longitudinal Cohort of Hematological Diseases (NICHE, NCT04645199) and described the clinical features and outcomes of AA after infecting Omicron SARS-CoV-2 between December 2022 and January 2023. This study demonstrated a low risk of relapse in AA after Omicron infection.In this study, SARS-CoV-2 illness severity was evaluated by the National Institutes of Health COVID-19 Treatment Guidelines. Severe illness was defined as individuals who had SpO 2 < 94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen <300 mmHg, a respiratory rate > 30 breaths/min, or lung infiltrates >50%. Hematological responses were evaluated based on established criteria. 9 Robust response was defined as not only meeting standard response criteria, 9 but fulfilling more than 50 Â 10 9 /L of platelet and 100 g/L of hemoglobin (Hb). A progressive and substantial decline in blood counts requiring reinitiation of highdose cyclosporine or androgen or thrombopoietin receptor agonists was defined as relapse. Paired t-tests were used to compare the hematological indices before and after Omicron infection, including Hb, platelet, neutrophil, and lymphocyte counts.The study engaged a total of 175 patients, comprising 90 males and 85 females, with a median age of 33 years (range, 10-72). Among these patients, 29.7% had SAA/VSAA, 14.3% had transfusiondependent AA, and 56.0% had transfusion-independent AA. Forty-six