We previously reported peptide vaccine candidates for HLA-A3 supertype (-A3, -A11, -A31, -A33)-positive cancer patients. In the present study, we examined whether those peptides can also induce cytotoxic T lymphocyte (CTL) activity restricted to HLA-A2, HLA-A24, and HLA-A26 alleles. Fourteen peptides were screened for their binding activity to HLA-A*0201, -A*0206, -A*0207, -A*2402, and -A*2601 molecules and then tested for their ability to induce CTL activity in peripheral blood mononuclear cells (PBMCs) from prostate cancer patients. Among these peptides, one from the prostate acid phosphatase protein exhibited binding activity to HLA-A*0201, -A*0206, and -A*2402 molecules. In addition, PBMCs stimulated with this peptide showed that HLA-A2 or HLA-A24 restricted CTL activity. Their cytotoxicity toward cancer cells was ascribed to peptide-specific and CD8+ T cells. These results suggest that this peptide could be widely applicable as a peptide vaccine for HLA-A3 supertype-, HLA-A2-, and -A24-positive cancer patients.

C35-44 peptide is a well known HLA-A2-restricted CTL epitope originating from hepatitis C virus (HCV) core protein. It was reported that the majority of HCV positive patients had significant levels of serum IgG specific to this peptide. This study addressed whether C35-44 peptide could induce CTL activity restricted to various HLA class IA alleles or could not. This peptide demonstrated binding activity to HLA-A*2402, -A*2601, -A*3101, and -A*3303 molecules, but not to HLA-A*1101 by means of stabilization assay. This peptide also induced CTL activity restricted to each of them, except HLA-A11(+) peripheral blood mononuclear cells from HCV 1b(+) patients by means of (51)Cr-release assay. With regard to HLA-A2 subtypes, this peptide demonstrated binding activity to HLA-A*0201 and -A*0206, but not to -A*0207 molecules. Furthermore, this peptide induced CTL activity from both the patients and healthy donors with all the HLA class IA molecules mentioned above by means of interferon-gamma production assay. These results may provide new insights for the development of a novel peptide vaccine against HCV compatible with various HLA class IA types.

One‐fifth of the Japanese population is positive for HLA‐A26, but few peptides are available as potential cancer vaccines for HLA‐A26‐positive cancer patients. The objective of this study was to identify peptide vaccine candidates for HLA‐A26‐positive cancer patients. The HLA‐A*2601‐crossbinding activity of 24 peptides currently under clinical trial as vaccines for HLA‐A2, ‐A24, or HLA‐A3 supertype–positive cancer patients was evaluated by stabilization assay. Three peptides with HLA‐A2‐binding activity could bind the HLA‐A*2601 molecule. These three peptides induced HLA‐A26‐restricted cytotoxic T lymphocytes from HLA‐A*2601‐, ‐A*2602‐, or ‐A*2603‐positive prostate cancer patients against HLA‐A*2601‐ and HLA‐A*2603‐positive cancer cells in CD8‐dependent and peptide‐specific manners. In addition, one peptide with HLA‐A24‐binding activity could bind to HLA‐A*2601 and induced HLA‐A26‐restricted cytotoxic T lymphocytes from HLA‐A*2601‐, ‐A*2602‐, or ‐A*2603‐positive prostate cancer patients against HLA‐A*2603‐positive cancer cells. These results may provide novel information for the development of a peptide‐based cancer vaccine for HLA‐A26‐positive patients.

Abstract. We previously reported the SART3 gene to be a tumor-rejection antigen gene encoding a peptide at positions [109][110][111][112][113][114][115][116][117][118] ) with the ability to induce HLA-A24-restricted cytotoxic T lymphocytes. In this study, we investigated both humoral and cellular responses to this peptide in cancer patients with alleles other than HLA-A24 to explore the possibility of using this peptide as a cancer vaccine for these patients. IgG reactive to SART3 109-118 peptide was identified in sera of the vast majority of non-cancer subjects (n=50) and all cancer patients (n=50) tested without apparent HLA-A association. Levels of anti-SART3 109-118 peptide antibody in cancer patients were significantly higher than those of non-cancer subjects, but no difference was found between HLA-A24 + A2 -and HLA-A24 -A2 + cancer patients. This peptide induced cancer cell-reactive cytotoxic T lymphocytes from peripheral blood mononuclear cells of both healthy donors and prostate cancer patients with HLA-A11, HLA-A31 and HLA-A33 alleles, but not with HLA-A2. These results suggest that this peptide can be applicable as a cancer vaccine not only for HLA-A24 + , but also for HLA-A11 + , HLA-A31 + and HLA-A33 + prostate cancer patients.

SARS-CoV-2 infection causes complicated clinic manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various tissues/organs examined, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Neuronal receptor NRP1 expression showed a significant induction by SARS-CoV-2 in cerebral cortex, which might be responsible for a higher infectivity and consequent inflammatory response. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.