Impact of aging and HIV infection on serologic response to seasonal influenza vaccination

Pallikkuth, Suresh; Armas, Lesley R. de; Pahwa, Rajendra; Rinaldi, Stefano; George, Valérie; Sanchez, Celeste M.; Li, Pan; Dickinson, Gordon M.; Rodríguez, Allan; Fischl, Margaret A.; Alcaide, María L.; Pahwa, Savita

doi:10.1097/qad.0000000000001774

Cited by 53 publications

(49 citation statements)

References 34 publications

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“…Serum antibody responses postvaccination showed the best responses (frequency and magnitude) in young uninfected participants, whereas a high proportion of old uninfected participants, as well as PWH of all age groups, were vaccine nonresponders (VNR). 49 Defects of B cells 50 and monocyte/macrophages 51 and association of inflammation and immune activation with VNR status 52 were also described. Interestingly, there was also a profound deficiency of influenza-specific and total peripheral T follicular helper (pTfh) cells in VNR and their pTfh cells exhibited markers of immune activation.…”

Section: Immune Dysregulation: Inflammation Activation Vaccine Respmentioning

confidence: 99%

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

Montano

Bhasin

D’Aquila

et al. 2019

AIDS Research and Human Retroviruses

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People aging with HIV (PAWH) infection experience greater impairments in physical and cognitive function, in addition to higher rates of peripheral comorbid conditions (e.g., renal failure, diabetes, bone fracture, hypertension, cardiovascular disease, polypharmacy, and multimorbidity). While multifactorial drivers, including HIV infection itself, antiretroviral therapy-related toxicities, disparities in care, and biobehavioral factors, likely contribute, there remains an overarching question as to what are the relevant age-related mechanisms and models that could inform interventions that promote health span and life span in PAWH? This workshop was convened to hear from experts on the biology of aging and HIV researchers studying PAWH to focus on advancing investigations at the interface of HIV and Aging. In this study, we summarize the discussions from the Harvard Center for AIDS Research and Boston Claude D. Pepper cosponsored workshop on HIV and Aging, which took place in October 2018.

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Section: Immune Dysregulation: Inflammation Activation Vaccine Respmentioning

confidence: 99%

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

Montano

Bhasin

D’Aquila

et al. 2019

AIDS Research and Human Retroviruses

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“…12 individuals were selected from a cohort of HIV-infected and healthy control adult volunteers (age range 60–76 yrs.) participating in an influenza vaccination study (FLORAH cohort) 15 to evaluate gene profiles of ex vivo H1N1-specific B cells (Table 1). All HIV-infected participants were virologically suppressed on ART.…”

Section: Resultsmentioning

confidence: 99%

“…Increase in serum titers of anti-influenza antibodies is a measure of immune response to the vaccination. We have previously shown that influenza-specific responses in B cells 14,15 , T cells 16–18 , and the innate immune system 19 are impaired in HIV-infected individuals in the context of viral suppression by ART in both young and old (>60 years) individuals. However, these studies have largely been performed using bulk cell analysis from in vitro antigen-stimulated culture experiments.…”

Section: Introductionmentioning

confidence: 99%

Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy

Armas

Pallikkuth

et al. 2019

Sci Rep

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Memory B cells (MBC) respond to secondary antigen challenge to protect against infection and to boost immunity following vaccinations. Despite effective treatment, chronic HIV infection disturbs MBCs by reducing numbers and altering functionality due to hyper-activation and increased apoptosis leading to suboptimal antibody responses against common infectious agents. We used single cell gene expression analysis to evaluate antigen-specific memory B cells in peripheral blood of virally-suppressed HIV-infected individuals and healthy controls stratified by serum H1N1 antibody response 3 weeks post-administration of the seasonal trivalent inactivated influenza vaccine. We used a fluorescent probe to isolate influenza H1N1-specific B cells and a multiplexed and targeted RT-PCR approach to measure expression levels of 96 genes involved in B cell activation and function. Gene profiling revealed a 4-gene predictive signature containing the phosphoinositide-3 kinase (PI3K) inhibitor, PTEN , for identifying antigen-specific MBC from HIV-infected individuals compared to healthy controls. Gene co-expression analysis showed that in addition to overexpression of PTEN , there was increased co-expression of type I interferon-associated genes with PTEN on single cell level in HIV compared to controls. This study highlights the persistent defects in MBC from HIV-infected individuals and points to the PI3K signaling pathway as a target for potential immune intervention.

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“…This limitation can be circumvented by including longitudinal samples over an extended period to determine the changes in the phenotypes and functions of T cells from these virologically controlled HIV-infected aging patients. Our study showed recovery from terminal differentiation of T cells with improved T cell functions, which may have implications on developing new modalities for HIV treatment, and in controlling acute and chronic infections and improving efficacy of vaccinations [ 33 ] in HIV+ patients with controlled viremia.…”

Section: Discussionmentioning

confidence: 97%

Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy

Behrens¹,

Wertheimer²,

Klotz³

et al. 2018

PLoS ONE

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Several studies have shown an increased accumulation of terminally differentiated T cells during HIV infection, suggestive of exhaustion/senescence, causing dysregulation of T cell homeostasis and function and rapid HIV disease progression. We have investigated whether long-term antiretroviral therapy (ART), which controls viremia and restores CD4 T cell counts, is correlated with reduction in terminally differentiated T cells, improved ratios of naïve to memory and function of T cells in 100 virologically controlled HIV-infected patients. We show that while the median frequencies of terminally differentiated CD4+ and CD8+ T cells (CD28-, CD27-, CD57+ and CD28-CD57+), were higher in the virologically controlled HIV-infected patients’ cohort compared with uninfected individuals’ cohort, the frequencies of these cells significantly decreased with increasing CD4 T cell counts in HIV-infected patients. Although, the naïve CD4+ and CD8+ T cells were lower in HIV patients’ cohort than uninfected cohort, there was a significant increase in both naïve CD4+ and CD8+ T cells with increasing CD4 T cell counts in HIV-infected patients. The underlying mechanism behind this increased naïve CD4+ and CD8+ T cells in HIV-infected patients was due to an increase in recent thymic emigrants, CD4+CD31+, as compared to CD4+CD31-. The CD4+ T cells of HIV-infected patients produced cytokines, including IL-2, IL-10 and IFN-γ comparable to uninfected individuals. In conclusion, virologically controlled HIV-infected patients on long-term ART show a significant reduction in terminally differentiated T cells, suggestive of decreased exhaustion/senescence, and improvement in the ratios of naïve to memory and function of T cells.

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Impact of aging and HIV infection on serologic response to seasonal influenza vaccination

Cited by 53 publications

References 34 publications

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy

Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy

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