Tfh Dysfunction in HIV and Aging

Study Overview
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Brief Summary
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The purpose of this research is to evaluate blood samples from HIV infected and non-HIV infected people to understand how aging and HIV infection affect the immune responses (body defenses against infection) to the flu vaccine.

Official Title
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Tfh Dysfunction in HIV and Aging

Conditions
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Human Influenza

Intervention / Treatment
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* Biological: Standard dose influenza vaccination
* Biological: High dose influenza vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For HIV positive participants: HIV infection, as documented by any licensed ELISA test kit. Participants on ART as a result of prior HIV documented infection will not be required to provide proof of diagnosis of HIV infection. Additional criteria for HIV positive on ART for at least 1 year. Occasional viral blips up to 1000 copies/ml also acceptable provided the patients are on continuing treatment, Cluster of differentiation 4 (CD4) count available in the prior 6 months and >200/mm3 Undetectable viral load (< 40 copies/mL). Blips of <1000 copies/mL will be allowed. For HIV negative participants: Documented negative HIV test at the time of study entry, either by any licensed ELISA. For all participants: Individuals age: ≤35 years and ≥65 years. No history of other immunodeficiency disorders Not on steroid or other immunosuppressive/immunomodulators medications. No active malignancies. Agreeable to receive both regular standard (STD-TIV) and high dose (HD-TIV) influenza vaccination. Agreeable to participate in study for a complete course of study full visits including 2 consecutive flu seasons. Able to provide informed consent. Exclusion criteria Contraindication to receive influenza vaccination. Non-adherence to ART for HIV positive Unable to provide informed consent. Influenza vaccination already given during the current vaccination season. Known drug abuse including cocaine by history

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Young HIV negative group<br>HIV uninfected participants that are 18-35 years of age will receive the standard dose flu vaccine. Participants who did not respond to the standard dose flu vaccination, as defined by less than a four-fold increase in flu antibody titer from baseline, will then receive the high dose flu vaccination 1 year after initial standard dose flu vaccination. Participants who respond to the standard dose flu vaccination will not receive the high dose flu vaccination. | Biological: Standard dose influenza vaccination<br>* Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone quadrivalent;Biological: High dose influenza vaccination<br>* 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone high dose quadrivalent;|
| Experimental: Young HIV positive group<br>HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 18-35 years of age, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose. | Biological: Standard dose influenza vaccination<br>* Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone quadrivalent;Biological: High dose influenza vaccination<br>* 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone high dose quadrivalent;|
| Experimental: Old HIV negative group<br>HIV uninfected participants that are 65 years and older will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose. | Biological: Standard dose influenza vaccination<br>* Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone quadrivalent;Biological: High dose influenza vaccination<br>* 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone high dose quadrivalent;|
| Experimental: Old HIV positive group<br>HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 65 years and older, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose. | Biological: Standard dose influenza vaccination<br>* Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone quadrivalent;Biological: High dose influenza vaccination<br>* 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle<br>* Other names: Fluzone high dose quadrivalent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HAI antibody response | Change in mean titers of Hemagglutination inhibition (HAI) antibody response will be measured using serum sample. | Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination) | 
| Change in neutralization antibody response | Change in mean titers of neutralization antibody response will be measured using serum sample. | Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination) | 
| Percentage of Participants with Vaccine Response | Percentage of participants that are vaccine responders and non-responders will be reported. Response is evaluated using seroconversion to the flu vaccine using serum sample. | Month 13 (1 month post high-dose flu vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of T-follicular helper (Tfh) cells | Percentage of Tfh cells as measured using peripheral blood samples | Month 13 (1 month post high-dose flu vaccination) | 
| Percentage of B cells | Percentage of B cells as measured using peripheral blood samples | Month 13 (1 month post high-dose flu vaccination) | 
| Percentage of monocytes | Percentage of monocytes as measured using peripheral blood samples | Month 13 (1 month post high-dose flu vaccination) | 
| Percentage of Tfh cells producing cytokines | Percentage of Tfh cells producing cytokines as measured using peripheral blood samples | Month 13 (1 month post high-dose flu vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Aging, flu vaccination, high dose vaccination, immune function