Enhancing T-cell responses to vaccination of HIV-1 infected subjects on antiretroviral therapy.

Format:

Book

Thesis/Dissertation

Author/Creator:

Ramirez, Lorenzo, author.

Contributor:

Boyer, Jean D., degree supervisor.

University of Pennsylvania. Cell and Molecular Biology.

Language:

English

Subjects (All):

Immunology.

Virology.

Cell and Molecular Biology--Penn dissertations.

Penn dissertations--Cell and Molecular Biology.

Local Subjects:

Immunology.

Virology.

Cell and Molecular Biology--Penn dissertations.

Penn dissertations--Cell and Molecular Biology.

Genre:

Academic theses.

Physical Description:

1 online resource (175 pages)

Contained In:

Dissertation Abstracts International 76-05B(E).

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor, MI : ProQuest, 2014.

System Details:

Mode of access: World Wide Web.

text file

Summary:

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-gamma 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 (15&mgr;g; 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 naive 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.

Notes:

Source: Dissertation Abstracts International, Volume: 76-05(E), Section: B.

Adviser: Jean D. Boyer.

Department: Cell and Molecular Biology.

Thesis Ph.D. University of Pennsylvania 2014.

Local Notes:

School code: 0175.

ISBN:

9781321480092

Access Restriction:

Restricted for use by site license.