First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies

PRRSV, the virus

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-strand RNA virus that belongs to the Arteriviridae family. PRRSV grows in primary alveolar macrophages and in monkey kidney cell lines. The genomic RNA is approximately 15 kb. The genome encodes the RNA replicase (ORF1a and ORF1b), the glycoproteins GP$_2$ to GP$_5$, the integral membrane protein M, and the nucleocapsid protein N (ORFs 2 to 7). A comparison of nucleotide sequences of different strains indicates that European and North American strains represent two distinct antigenic types. Various PRRSV-specific monoclonal antibodies and recombinant structural proteins have been produced. Well-defined PRRSV mutants can be generated with the recently developed infectious cDNA clone of PRRSV.Syndrome dysgénésique et respiratoire porcin, le virus. Le virus du syndrome dysgénésique et respiratoire porcin (PRRSV) est un virus à ARN simple brin de polarité positive qui appartient à la famille des Arteriviridae. PRRSV se multiplie sur des macrophages alvéolaires et sur des lignées cellulaires dérivées de rein de singe. L'ARN génomique est d'une longueur approximative de 15 kb. Le génome code pour la réplicase de l'ARN (ORF1a et ORF1b), les glycoprotéines GP$_2$ à GP$_5$, la protéine membranaire intégrale M, et la protéine de nucléocapside N (ORFs 2 à 7). La comparaison des séquences nucléotidiques des différentes souches indique que les souches européenne et nord-américaine représentent deux types antigéniques distincts. Divers anticorps monoclonaux spécifiques du PRRSV, et diverses protéines de structure recombinantes ont été obtenus. Des mutants bien définis du PRRSV peuvent être produits grâce au clone d'ADNc infectieux du PRRSV qui a été récemment construit