{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/28222"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/28222","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"Enhancing T-Cell Responses to Vaccination of HIV-1 infected Subjects on Antiretroviral Therapy","abstract":"With the advancement in anti-retroviral therapy (ART) regimens there has been a significant improvement in the quality of life and survival of those individuals infected with HIV-1. Even with the benefits to CD4+ cell counts, decrease in viremia and inflammatory biomarkers, HIV-1 infected individuals continue to exhibit functional issues in their T-cell immune responses to recall antigens and vaccines. Additionally, researchers believe that T-cell mediated responses will be important to elicit in a therapeutic vaccination setting. These T-cell functionality issues can leave individuals infected with HIV-1 at risk from opportunistic infections and co-morbidities. Furthermore, a therapeutic HIV-1 vaccine is needed that can elicit responses to help infected subjects better control HIV infection so as to potentially reduce the need for long-term therapy. However, basic research on HIV is still needed to solidify potential immune correlates against HIV and other pathogens affecting HIV-1 infected subjects. Likewise, investigation of therapeutic targets that can aid in enhancing T-cell immune responses in these individuals is of importance. In this thesis, we examined whether a therapeutic HIV-1 DNA vaccine delivered with in vivo electroporation to HIV-1 infected subjects on ART could elicit potent cellular immune responses previously suggested to be important in the control of HIV. This vaccine strategy demonstrated an enhancement in cell-mediated IFN-γ production and cytotoxic immune responses to HIV-1. However, until a vaccine or therapy for HIV-1 is developed, these individuals also continue to be at risk for other opportunistic infections, such as influenza infection. Supported by previous studies that focus on influenza vaccination, we found that a standard dose of the H1N1 vaccine (15μg; Novartis) did not elicit sero-protection in all individuals. Importantly, the ability of these individuals to respond to vaccination was associated with the frequency of naïve CD4+ T-cells prior to vaccination, thereby reinforcing the importance of CD4+ T-cell help and the need for better CD4+ T-cell reconstitution. In addition, HIV-1 infected subjects, despite ART, have an altered cytokine/chemokine environment. Thereby it is important to explore whether targeting the cytokine milieu can lead to improvements in responses to vaccination in these individuals. We specifically found that the pro-inflammatory chemokine IP-10 was elevated in the sera of those infected with HIV-1 while on ART. Additionally, elevated levels of IP-10 were associated with decreased cellular immune responses, which could be improved by neutralizing IP-10 prior to antigen stimulation. Therefore, the studies herein support the need for better understanding of the basic science of HIV-1 infection to uncover and comprehend what potential immune correlates are needed for therapeutic treatment of these individuals.","abstract_html":"With the advancement in anti-retroviral therapy (ART) regimens there has been a significant improvement in the quality of life and survival of those individuals infected with HIV-1. Even with the benefits to CD4+ cell counts, decrease in viremia and inflammatory biomarkers, HIV-1 infected individuals continue to exhibit functional issues in their T-cell immune responses to recall antigens and vaccines. Additionally, researchers believe that T-cell mediated responses will be important to elicit in a therapeutic vaccination setting. These T-cell functionality issues can leave individuals infected with HIV-1 at risk from opportunistic infections and co-morbidities. Furthermore, a therapeutic HIV-1 vaccine is needed that can elicit responses to help infected subjects better control HIV infection so as to potentially reduce the need for long-term therapy. However, basic research on HIV is still needed to solidify potential immune correlates against HIV and other pathogens affecting HIV-1 infected subjects. Likewise, investigation of therapeutic targets that can aid in enhancing T-cell immune responses in these individuals is of importance. In this thesis, we examined whether a therapeutic HIV-1 DNA vaccine delivered with in vivo electroporation to HIV-1 infected subjects on ART could elicit potent cellular immune responses previously suggested to be important in the control of HIV. This vaccine strategy demonstrated an enhancement in cell-mediated IFN-γ production and cytotoxic immune responses to HIV-1. However, until a vaccine or therapy for HIV-1 is developed, these individuals also continue to be at risk for other opportunistic infections, such as influenza infection. Supported by previous studies that focus on influenza vaccination, we found that a standard dose of the H1N1 vaccine (15μg; Novartis) did not elicit sero-protection in all individuals. Importantly, the ability of these individuals to respond to vaccination was associated with the frequency of naïve CD4+ T-cells prior to vaccination, thereby reinforcing the importance of CD4+ T-cell help and the need for better CD4+ T-cell reconstitution. In addition, HIV-1 infected subjects, despite ART, have an altered cytokine/chemokine environment. Thereby it is important to explore whether targeting the cytokine milieu can lead to improvements in responses to vaccination in these individuals. We specifically found that the pro-inflammatory chemokine IP-10 was elevated in the sera of those infected with HIV-1 while on ART. Additionally, elevated levels of IP-10 were associated with decreased cellular immune responses, which could be improved by neutralizing IP-10 prior to antigen stimulation. Therefore, the studies herein support the need for better understanding of the basic science of HIV-1 infection to uncover and comprehend what potential immune correlates are needed for therapeutic treatment of these individuals.","abstract_has_math":false,"creators":["Ramirez, Lorenzo Antonio"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Jean D. Boyer"],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-01-01","date_published":"2014-01-01","updated_at":"2026-07-24T03:46:00Z","subjects":[],"languages":["en"],"rights":["Lorenzo Antonio Ramirez"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/28222","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Jean D. 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Even with the benefits to CD4+ cell counts, decrease in viremia and inflammatory biomarkers, HIV-1 infected individuals continue to exhibit functional issues in their T-cell immune responses to recall antigens and vaccines. Additionally, researchers believe that T-cell mediated responses will be important to elicit in a therapeutic vaccination setting. These T-cell functionality issues can leave individuals infected with HIV-1 at risk from opportunistic infections and co-morbidities. Furthermore, a therapeutic HIV-1 vaccine is needed that can elicit responses to help infected subjects better control HIV infection so as to potentially reduce the need for long-term therapy. However, basic research on HIV is still needed to solidify potential immune correlates against HIV and other pathogens affecting HIV-1 infected subjects. Likewise, investigation of therapeutic targets that can aid in enhancing T-cell immune responses in these individuals is of importance. In this thesis, we examined whether a therapeutic HIV-1 DNA vaccine delivered with in vivo electroporation to HIV-1 infected subjects on ART could elicit potent cellular immune responses previously suggested to be important in the control of HIV. This vaccine strategy demonstrated an enhancement in cell-mediated IFN-γ production and cytotoxic immune responses to HIV-1. However, until a vaccine or therapy for HIV-1 is developed, these individuals also continue to be at risk for other opportunistic infections, such as influenza infection. Supported by previous studies that focus on influenza vaccination, we found that a standard dose of the H1N1 vaccine (15μg; Novartis) did not elicit sero-protection in all individuals. Importantly, the ability of these individuals to respond to vaccination was associated with the frequency of naïve CD4+ T-cells prior to vaccination, thereby reinforcing the importance of CD4+ T-cell help and the need for better CD4+ T-cell reconstitution. In addition, HIV-1 infected subjects, despite ART, have an altered cytokine/chemokine environment. Thereby it is important to explore whether targeting the cytokine milieu can lead to improvements in responses to vaccination in these individuals. We specifically found that the pro-inflammatory chemokine IP-10 was elevated in the sera of those infected with HIV-1 while on ART. Additionally, elevated levels of IP-10 were associated with decreased cellular immune responses, which could be improved by neutralizing IP-10 prior to antigen stimulation. Therefore, the studies herein support the need for better understanding of the basic science of HIV-1 infection to uncover and comprehend what potential immune correlates are needed for therapeutic treatment of these individuals."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Enhancing T-Cell Responses to Vaccination of HIV-1 infected Subjects on Antiretroviral Therapy"]}]}],"canonical_facts":{"dc:contributor.advisor":["Jean D. Boyer"],"dc:creator":["Ramirez, Lorenzo Antonio"],"dc:date":["2023-05-17T12:53:21.000"],"dc:date.accessioned":["2023-05-22T16:33:07Z"],"dc:date.available":["2001-01-01T00:00:00Z"],"dc:date.issued":["2014-01-01"],"dc:description.abstract":["With the advancement in anti-retroviral therapy (ART) regimens there has been a significant improvement in the quality of life and survival of those individuals infected with HIV-1. Even with the benefits to CD4+ cell counts, decrease in viremia and inflammatory biomarkers, HIV-1 infected individuals continue to exhibit functional issues in their T-cell immune responses to recall antigens and vaccines. Additionally, researchers believe that T-cell mediated responses will be important to elicit in a therapeutic vaccination setting. These T-cell functionality issues can leave individuals infected with HIV-1 at risk from opportunistic infections and co-morbidities. Furthermore, a therapeutic HIV-1 vaccine is needed that can elicit responses to help infected subjects better control HIV infection so as to potentially reduce the need for long-term therapy. However, basic research on HIV is still needed to solidify potential immune correlates against HIV and other pathogens affecting HIV-1 infected subjects. Likewise, investigation of therapeutic targets that can aid in enhancing T-cell immune responses in these individuals is of importance. In this thesis, we examined whether a therapeutic HIV-1 DNA vaccine delivered with in vivo electroporation to HIV-1 infected subjects on ART could elicit potent cellular immune responses previously suggested to be important in the control of HIV. This vaccine strategy demonstrated an enhancement in cell-mediated IFN-γ production and cytotoxic immune responses to HIV-1. However, until a vaccine or therapy for HIV-1 is developed, these individuals also continue to be at risk for other opportunistic infections, such as influenza infection. Supported by previous studies that focus on influenza vaccination, we found that a standard dose of the H1N1 vaccine (15μg; Novartis) did not elicit sero-protection in all individuals. Importantly, the ability of these individuals to respond to vaccination was associated with the frequency of naïve CD4+ T-cells prior to vaccination, thereby reinforcing the importance of CD4+ T-cell help and the need for better CD4+ T-cell reconstitution. In addition, HIV-1 infected subjects, despite ART, have an altered cytokine/chemokine environment. Thereby it is important to explore whether targeting the cytokine milieu can lead to improvements in responses to vaccination in these individuals. We specifically found that the pro-inflammatory chemokine IP-10 was elevated in the sera of those infected with HIV-1 while on ART. Additionally, elevated levels of IP-10 were associated with decreased cellular immune responses, which could be improved by neutralizing IP-10 prior to antigen stimulation. Therefore, the studies herein support the need for better understanding of the basic science of HIV-1 infection to uncover and comprehend what potential immune correlates are needed for therapeutic treatment of these individuals."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/28222"],"dc:language":["en"],"dc:rights":["Lorenzo Antonio Ramirez"],"dc:title":["Enhancing T-Cell Responses to Vaccination of HIV-1 infected Subjects on Antiretroviral Therapy"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:46:00Z"}