PROCESS FOR PRODUCING A PROPHYLACTIC AND THERAPEUTIC DNA IMMUNOLOGICAL COMPOSITION FOR HPV AND CANCERS ASSOCIATED WITH THE VIRUS, HYBRID PROTEIN, EXPRESSION VECTOR, IMMUNOLOGICAL COMPOSITION AND USES THEREOF

• Main Authors: CIANCIARULLO, Aurora Marques, SASAKI, Érica Akemi Kavati
• Format: Patent
• Language: English; French; Portuguese
• Published: 10.06.2021
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

The present invention relates to a prophylactic and therapeutic vaccine for HPV and cancers associated with the virus, intended for people seeking prevention or for those already infected with HPV who have developed cancer. The present invention also relates to DNA expression vectors that can efficiently produce the HPV16 virus capsid protein L2 and also the viral oncoprotein E6 associated with human papillomavirus tumors. In particular, the present invention relates to the production of recombinant fusion or hybrid proteins, by means of gene cloning in expression vectors, said proteins being produced by gene translation of fused genes formed by combining nucleic acid regulatory sequences of one or more genes with the protein encoding sequences of one or more genes, and used for generating two distinct types of responses: a long-lasting humoral immune response, capable of stimulating the production of specific anti-L2 and anti-E6 antibodies against HPV (prophylactic action), and also the activation of a cellular immune response for fighting tumor cells and inducing the expression of TNF (Tumor Necrosis Factor) cytokines (therapeutic action). La présente invention concerne un vaccin prophylactique et thérapeutique contre le VPH et les cancers associés au virus, destinée aux personnes souhaitant une prévention ou à celles déjà infectées par le VPH ayant développé un cancer. L'invention concerne également des vecteurs d'expression d'ADN qui peuvent produire efficacement la protéine L2 du capside du virus VPH 16, outre l'oncoprotéine virale E6 associée aux tumeurs du papillomavirus humain. Plus particulièrement, l'invention concerne l'obtention de protéines recombinantes de fusion ou hybrides par clonage génique dans des vecteurs d'expression, produites par traduction génétique de gènes fusionnés, formés par combinaison de séquences régulatrices d'acides nucléiques d'un ou plusieurs gènes, avec les séquences codantes de protéine d'un ou plusieurs gènes, utilisées pour produire deux types distincts de réponses: réponse immunitaire humorale durable, capable de stimuler la production d'anticorps spécifiques anti-L2 et anti-E6 contre le VPH (action prophylactique), et d'activer la réponse immunitaire cellulaire en vue de combattre les cellules tumorales et d'induire l'expression de cytokines TNF (Tumor Necrosis Factor) ou facteur de nécrose tumorale (action thérapeutique). A presente invenção se refere à vacina profilática e terapêutica contra HPV e cânceres associados ao vírus, destinada a pessoas que buscam a prevenção ou àquelas já infectadas por HPV que desenvolveram câncer. Refere-se também a vetores de expressão de DNA que podem produzir eficientemente a proteína L2 do capsídeo do vírus HPV16, além da oncoproteína viral E6 associada a tumores do Papilomavírus humano. Em particular, esta invenção refere-se à obtenção de proteínas recombinantes de fusão ou híbridas, através da clonagem gênica em vetores de expressão, produzidas pela tradução genética de genes fundidos, formados pela combinação de sequências reguladoras de ácidos nucleicos de um ou mais genes, com as sequências codificadoras de proteína de um ou mais genes, empregadas para gerar dois tipos distintos de respostas: resposta imune humoral duradoura, capaz de estimular a produção de anticorpos específicos anti-L2 e anti-E6 contra HPV (ação profilática), assim como ativar a resposta imune celular, para combater as células tumorais e induzindo a expressão de citocinas TNF (Tumor Necrosis Factor) ou Fator de Necrose Tumoral (ação terapêutica).