Impact of aging on immunity in the context of COVID-19, HIV, and tuberculosis

Grifoni, Alba; Alonzi, Tonino; Alter, Galit; Noonan, Douglas M.; Landay, Alan; Albini, Adriana; Goletti, Delia

doi:10.3389/fimmu.2023.1146704

Cited by 26 publications

(15 citation statements)

References 213 publications

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“…While there is optimism regarding the potential of combination approaches, it is important to acknowledge that a scalable, clinically well-tolerated therapeutic strategy to either cure or control HIV in the absence of ART is unlikely to occur in the same timescale as has been proposed to end the HIV epidemic (ie, by 2030) [ 6 , 8 ]. As such, an emerging area of concern is to address how age-related perturbations in immune function and HIV-associated immunosenescence [ 162 – 164 ] intersect with the maintenance of infected cells during long-term ART [ 165 ], with the risk of co-morbidities [ 166 - 168 ], and with responsiveness to immune-based cure strategies [ 169 – 171 ]. Moreover, a portfolio of experimental and FDA-approved drugs are under investigation for their ability to either eliminate (ie, senolytics) or alter the function (ie, senomorphic) of senescent cells, including Bcl-2 inhibitors (Venetoclax), JAK1/JAK2 inhibitors (ruxolitinib), mTOR inhibitors (rapamycin), and tyrosine kinase inhibitors (dasatinib) among others [ 172 , 173 ]; however, further study is required to evaluate these agents for their utility in attenuating or reversing HIV-induced immunosenescence and affecting HIV persistence.…”

Section: Progress Towards a Curementioning

confidence: 99%

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Harper,

Betts,

Lichterfeld

et al. 2024

PAI

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Once a death sentence, HIV is now considered a manageable chronic disease due to the development of antiretroviral therapy (ART) regimens with minimal toxicity and a high barrier for genetic resistance. While highly effective in arresting AIDS progression and rendering the virus untransmissible in people living with HIV (PLWH) with undetectable viremia (U=U) [1, 2]), ART alone is incapable of eradicating the “reservoir” of resting, latently infected CD4+ T cells from which virus recrudesces upon treatment cessation. As of 2022 estimates, there are 39 million PLWH, of whom 86% are aware of their status and 76% are receiving ART [3]. As of 2017, ART-treated PLWH exhibit near normalized life expectancies without adjustment for socioeconomic differences [4]. Furthermore, there is a global deceleration in the rate of new infections [3] driven by expanded access to pre-exposure prophylaxis (PrEP), HIV testing in vulnerable populations, and by ART treatment [5]. Therefore, despite outstanding issues pertaining to cost and access in developing countries, there is strong enthusiasm that aggressive testing, treatment, and effective viral suppression may be able to halt the ongoing HIV epidemic (ie, UNAIDS’ 95-95-95 targets) [6–8]; especially as evidenced by recent encouraging observations in Sydney [9]. Despite these promising efforts to limit further viral transmission, for PLWH, a “cure” remains elusive; whether it be to completely eradicate the viral reservoir (ie, cure) or to induce long-term viral remission in the absence of ART (ie, control; Figure 1). In a previous salon hosted by Pathogens and Immunity in 2016 [10], some researchers were optimistic that a cure was a feasible, scalable goal, albeit with no clear consensus on the best route. So, how are these cure strategies panning out? In this commentary, 8 years later, we will provide a brief overview on recent advances and failures towards identifying determinants of viral persistence and developing a scalable cure for HIV. Based on these observations, and as in the earlier salon, we have asked several prominent HIV cure researchers for their perspectives.

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Section: Progress Towards a Curementioning

confidence: 99%

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Harper,

Betts,

Lichterfeld

et al. 2024

PAI

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“…Additionally, there was minimal effect of age on the relationship between vitamin D levels and SARS-CoV-2 infection. Given the findings in extant literature that demonstrates age-related immune function changes and increases in the risk of SARS-CoV-2 infection among older adults [ 21 ], this finding warrants further examination in future studies.…”

Section: Discussionmentioning

confidence: 89%

Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study

Coudray,

Hansel,

Alesci

et al. 2024

Viruses

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Background: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States. Methods: We conducted a descriptive analysis to explore the relationship between vitamin D levels and SARS-CoV-2 infection among medically underserved participants. A combined molecular and serologic assessment was used to determine the prevalence of SARS-CoV-2 infection. Vitamin D was examined as both a categorical (vitamin D status: deficient, insufficient, optimal) and continuous (vitamin D level) variable. Chi-squared testing, polynomial regression models, and logistic regression models were used to assess the relationship between vitamin D and SARS-CoV-2 infection. Results: The overall SARS-CoV-2 infection rate among participants was 25.9%. Most participants were either vitamin D deficient (46.5%) or insufficient (29.7%), and 23.8% had an optimal level. Vitamin D status was significantly associated with key SARS-CoV-2 infection risk factors. As mean vitamin D levels increased, the proportion of participants with SARS-CoV-2 infection decreased. For every 10 ng/mL increase in vitamin D levels the odds of SARS-CoV-2 infection decreased by 12% when adjusting for race/ethnicity and age (main effect model). Participants who identified as Hispanic/Latino or Black non-Hispanic had approximately two times increased odds of SARS-CoV-2 infection when adjusting for age and vitamin D levels compared to white non-Hispanics. However, when additional factors were added to the main effect model, the relationship between vitamin D levels and SARS-CoV-2 infection did not remain significant. Conclusion: Vitamin D levels were associated with an increased risk of SARS-CoV-2 infection. Hispanic/Latino and Black, non-Hispanic compared to White, non-Hispanic participants were at increased odds for infection, after adjusting for race/ethnicity and age.

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“…Life extension of the world population is leading to an increase in age-associated diseases, including a higher susceptibility to infections. This issue became evident during the early phase of the COVID-19 pandemic, when the elderly population was severely hit 6 , 30 . As soon as the first SARS-CoV-2 vaccines became available, the elderly, immunosuppressed and people with comorbidities were prioritised 9 .…”

Section: Discussionmentioning

confidence: 99%

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models

Usai,

Ainsua-Enrich,

Gales

et al. 2024

npj Vaccines

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Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22–23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

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Impact of aging on immunity in the context of COVID-19, HIV, and tuberculosis

Cited by 26 publications

References 213 publications

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models

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