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To explore the immunogenicity of IDH1(R132H), 10-merand 15-mer peptide libraries were generated encompassing the mutated (R132H) and the corresponding wild-type residue of human IDH1 (Extended Data Fig. 1a-c). Neither interrogation [...], Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas (1-3) and other types of tumour (4-6). They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG) (7,8), genomic hypermethylation (9-11), genetic instability and malignant transformation (12). More than 70% of diffuse grade II and grade III gliomas carry the most frequent mutation, IDH1(R132H) (ref. 3). From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells (13,14). Here we demonstrate that IDH1(R132H) contains an immunogenic epitope suitable for mutation-specific vaccination. Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific [CD4.sup.+] T-helper-1 ([T.sub.H]1) responses. [CD4.sup.+] [T.sub.H]1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H). Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a [CD4.sup.+] T-cell-dependent manner. As IDH1(R132H) is presentin all tumour cells of these slow-growing gliomas (15), a mutation-specific anti-IDH1(R132H) vaccine may represent a viable novel therapeutic strategy for IDH1(R132H)-mutated tumours.

Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines. [ABSTRACT FROM AUTHOR]

Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines. [ABSTRACT FROM AUTHOR]

High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches.