Publicação
Development and pre-clinical evaluation of a new HIV-1 vaccine concept
| Resumo: | New 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. |
|---|---|
| Autores principais: | Calado, Rita |
| Assunto: | Teses de doutoramento - 2018 |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866809780403699712 |
|---|---|
| author | Calado, Rita |
| author_facet | Calado, Rita |
| author_role | author |
| contributor_name_str_mv | Taveira, Nuno, 1964- Pereira, J. Moniz, 1949- Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Calado, Rita\",\"Person.identifier.orcid\":\"0000-0002-2519-7917\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Taveira, Nuno, 1964- Pereira, J. Moniz, 1949- Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Calado, Rita |
| datacite.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2019-01-22T01:30:16Z |
| datacite.date.embargoed.fl_str_mv | 2019-01-22T01:30:16Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Teses de doutoramento - 2018 |
| datacite.titles.title.fl_str_mv | Development and pre-clinical evaluation of a new HIV-1 vaccine concept |
| dc.contributor.none.fl_str_mv | Taveira, Nuno, 1964- Pereira, J. Moniz, 1949- Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Calado, Rita |
| dc.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2019-01-22T01:30:16Z |
| dc.date.embargoed.fl_str_mv | 2019-01-22T01:30:16Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/32686 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Teses de doutoramento - 2018 |
| dc.title.fl_str_mv | Development and pre-clinical evaluation of a new HIV-1 vaccine concept |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_db06 |
| description | New 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/6dfdb847-d974-4cd1-b1a6-8ff3184bd51a/download |
| funding.funder.alternateName_str_mv | FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia |
| id | ul_c83c5cf8d4c4f77fa072e3345d5facf0 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/32686 |
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| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
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| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/32686 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Calado, Rita Calado, Rita https://www.ciencia-id.pt/AA18-62FA-B4B3 AA18-62FA-B4B3 http://orcid.org/0000-0002-2519-7917 0000-0002-2519-7917 |
| publishDate | 2018 |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engpt_PTNew 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.application/pdfpt_PTDevelopment and pre-clinical evaluation of a new HIV-1 vaccine conceptPersonalCalado, RitaDSpacehttp://dspace.org/items/bca88dd5-4b60-4441-93dd-eddfa6fa50efDSpacehttp://dspace.org/items/bca88dd5-4b60-4441-93dd-eddfa6fa50efAlmeida CaladoRita DiogoCiência IDhttps://www.ciencia-id.ptAA18-62FA-B4B3ORCIDhttp://orcid.org0000-0002-2519-7917Taveira, Nuno, 1964-Pereira, J. Moniz, 1949-HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptURNurn:tid:1013759212019-01-22T01:30:16Z201820182018-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/32686http://purl.org/coar/access_right/c_abf2open accessTeses de doutoramento - 20185276561 bytesFundação para a Ciência e a TecnologiaDEVELOPMENT AND PRE-CLINICAL EVALUATION OF A NEW HIV-1 VACCINE CONCEPTCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_db06doctoral thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/6dfdb847-d974-4cd1-b1a6-8ff3184bd51a/download |
| spellingShingle | Development and pre-clinical evaluation of a new HIV-1 vaccine concept Calado, Rita Teses de doutoramento - 2018 |
| status | SINGLETON |
| subject.fl_str_mv | Teses de doutoramento - 2018 |
| title | 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_short | 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 |
| topic | Teses de doutoramento - 2018 |
| topic_facet | Teses de doutoramento - 2018 |
| url | http://hdl.handle.net/10451/32686 |
| visible | 1 |