Development and pre-clinical evaluation of a new HIV-1 vaccine concept

Detalhes bibliográficos
Autor(a) principal: Calado, Rita
Data de Publicação: 2018
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10451/32686
Resumo: Tese de doutoramento, Farmácia (Microbiologia), Universidade de Lisboa, Faculdade de Farmácia, 2018
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spelling Development and pre-clinical evaluation of a new HIV-1 vaccine conceptTeses de doutoramento - 2018Domínio/Área Científica::Ciências Médicas::Medicina BásicaTese de doutoramento, Farmácia (Microbiologia), Universidade de Lisboa, Faculdade de Farmácia, 2018New immunogens that elicit the production of broadly neutralizing antibodies (bNAbs) are needed to prevent and control HIV-1 epidemic. However, their induction by vaccination is still a difficult task. Prime-boost immunization strategies combining poxvirus with envelope glycoproteins constitutes a promising approach for an HIV-1 preventive vaccine as they provide strong immune responses. Recently, bNAbs against HIV-2 were elicited in mice using a Vaccinia vector-prime C2V3C3 polypeptide boost vaccination strategy. Thus, the main goal of this thesis was to determine if a similar strategy would elicit the production of bNAbs against HIV-1. The general aims of this thesis were: obtain and examine HIV-1 samples derived from Angolan isolates as a paradigm of the ancestral viruses we intended to use in a new type of vaccine, express envelope genes from Angolan and Portuguese isolates in Vaccinia virus and produce the autologous C2V3C3 recombinant polypeptides, investigate the immunogenicity of these immunogens in mice and rabbits using different regimens and quantify the respective cellular immune responses. In chapter 2, three full-length genomes from Angolan patients were sequenced and analyzed in order to better understand the origin and dynamics of HIV-1 in Angola. A pure subtype J, a subtype J with a small uncertain region and the first H/U/CRF02_AG recombinant were identified. Overall, these results supported the extraordinary genetic diversity of HIV-1 and confirm the ancestral presence of this subtypes in Angola. In chapters 3, gp120 glycoproteins expressed in Vaccinia virus, soluble gp120 and C2V3C3 polypeptides derived from several HIV-1 isolates from Angola and Portugal (clades B, C, CRF02_AG and J) were produced and used as immunogens in mice and rabbits (chapter 4). CRF02_AG based immunogens were able to elicit bNAbs against several heterologous HIV-1 tier 2 viruses and V3 region was found to be one of the main target of this immunogen. Antibody responses were associated with adequate Tfh and Tfr responses indicating that this strategy targeted the cellular subsets required for the induction of an effective NAb response. In conclusion, the results obtained suggest that the novel CRF02_AG based immunogens and primeboost immunization strategy may be able to induce the type of response intended in a preventive HIV-1 vaccine.Taveira, Nuno, 1964-Pereira, J. Moniz, 1949-Repositório da Universidade de LisboaCalado, Rita2019-01-22T01:30:16Z201820182018-01-01T00:00:00Zdoctoral thesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10451/32686TID:101375921enginfo:eu-repo/semantics/embargoedAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T13:52:01Zoai:repositorio.ulisboa.pt:10451/32686Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T02:56:32.997090Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Development and pre-clinical evaluation of a new HIV-1 vaccine concept
title Development and pre-clinical evaluation of a new HIV-1 vaccine concept
spellingShingle Development and pre-clinical evaluation of a new HIV-1 vaccine concept
Calado, Rita
Teses de doutoramento - 2018
Domínio/Área Científica::Ciências Médicas::Medicina Básica
title_short Development and pre-clinical evaluation of a new HIV-1 vaccine concept
title_full Development and pre-clinical evaluation of a new HIV-1 vaccine concept
title_fullStr Development and pre-clinical evaluation of a new HIV-1 vaccine concept
title_full_unstemmed Development and pre-clinical evaluation of a new HIV-1 vaccine concept
title_sort Development and pre-clinical evaluation of a new HIV-1 vaccine concept
author Calado, Rita
author_facet Calado, Rita
author_role author
dc.contributor.none.fl_str_mv Taveira, Nuno, 1964-
Pereira, J. Moniz, 1949-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Calado, Rita
dc.subject.por.fl_str_mv Teses de doutoramento - 2018
Domínio/Área Científica::Ciências Médicas::Medicina Básica
topic Teses de doutoramento - 2018
Domínio/Área Científica::Ciências Médicas::Medicina Básica
description Tese de doutoramento, Farmácia (Microbiologia), Universidade de Lisboa, Faculdade de Farmácia, 2018
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018-01-01T00:00:00Z
2019-01-22T01:30:16Z
dc.type.driver.fl_str_mv doctoral thesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/32686
TID:101375921
url http://hdl.handle.net/10451/32686
identifier_str_mv TID:101375921
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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