The Impact of Immuno-aging on SARS-CoV-2 Vaccine Development

Overview

Journal Geroscience

Specialty Geriatrics

Date 2021 Feb 11

PMID 33569701

Citations 20

Authors

Jennifer Connors

Matthew R Bell

Jennifer Marcy

Michele Kutzler

Elias K Haddad

Affiliations

Soon will be listed here.

Abstract

The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.

Citing Articles

Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV.

Ray S, Narayanan A, Vesterbacka J, Blennow O, Chen P, Gao Y NPJ Biofilms Microbiomes. 2023; 9(1):104.

PMID: 38123600 PMC: 10733305. DOI: 10.1038/s41522-023-00461-w.

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age.

Orillard E, Spehner L, Mansi L, Bouard A, Falcoz A, Lepiller Q Front Immunol. 2023; 14:1160664.

PMID: 37334387 PMC: 10272422. DOI: 10.3389/fimmu.2023.1160664.

Korean Red Ginseng Potentially Improves Maintaining Antibodies after COVID-19 Vaccination: A 24-Week Longitudinal Study.

Yoon J, Park B, Kim H, Choi S, Jung D Nutrients. 2023; 15(7).

PMID: 37049424 PMC: 10097014. DOI: 10.3390/nu15071584.

"Just right" combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation.

Ananya A, Holden K, Gu Z, Nettleton D, Mallapragada S, Wannemuehler M Immun Ageing. 2023; 20(1):10.

PMID: 36895007 PMC: 9996592. DOI: 10.1186/s12979-023-00332-0.

Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home.

Pozo-Balado M, Bulnes-Ramos A, Olivas-Martinez I, Garrido-Rodriguez V, Lozano C, Alvarez-Rios A Immun Ageing. 2023; 20(1):9.

PMID: 36879319 PMC: 9986663. DOI: 10.1186/s12979-023-00334-y.

References

Goodwin K, Viboud C, Simonsen L . Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. 2005; 24(8):1159-69. DOI: 10.1016/j.vaccine.2005.08.105. View

Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S . Inflammaging and 'Garb-aging'. Trends Endocrinol Metab. 2016; 28(3):199-212. DOI: 10.1016/j.tem.2016.09.005. View

Ferrucci L, Fabbri E . Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018; 15(9):505-522. PMC: 6146930. DOI: 10.1038/s41569-018-0064-2. View

Vukmanovic-Stejic M, Chambers E, Suarez-Farinas M, Sandhu D, Fuentes-Duculan J, Patel N . Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation. J Allergy Clin Immunol. 2017; 142(3):844-856. PMC: 6127037. DOI: 10.1016/j.jaci.2017.10.032. View

Swift M, Burns A, Gray K, DiPietro L . Age-related alterations in the inflammatory response to dermal injury. J Invest Dermatol. 2001; 117(5):1027-35. DOI: 10.1046/j.0022-202x.2001.01539.x. View

Verschoor C, Johnstone J, Loeb M, Bramson J, Bowdish D . Anti-pneumococcal deficits of monocyte-derived macrophages from the advanced-age, frail elderly and related impairments in PI3K-AKT signaling. Hum Immunol. 2014; 75(12):1192-6. DOI: 10.1016/j.humimm.2014.10.004. View

Mitzel D, Lowry V, Shirali A, Liu Y, Stout-Delgado H . Age-enhanced endoplasmic reticulum stress contributes to increased Atg9A inhibition of STING-mediated IFN-β production during Streptococcus pneumoniae infection. J Immunol. 2014; 192(9):4273-83. PMC: 4007355. DOI: 10.4049/jimmunol.1303090. View

Kong K, Wang X, Anderson J, Fikrig E, Montgomery R . West nile virus attenuates activation of primary human macrophages. Viral Immunol. 2008; 21(1):78-82. PMC: 2666911. DOI: 10.1089/vim.2007.0072. View

Kong K, Delroux K, Wang X, Qian F, Arjona A, Malawista S . Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly. J Virol. 2008; 82(15):7613-23. PMC: 2493309. DOI: 10.1128/JVI.00618-08. View

10.

Brown B, Sicari B, Badylak S . Rethinking regenerative medicine: a macrophage-centered approach. Front Immunol. 2014; 5:510. PMC: 4219501. DOI: 10.3389/fimmu.2014.00510. View

11.

Albright J, Dunn R, Shults J, Boe D, Afshar M, Kovacs E . Advanced Age Alters Monocyte and Macrophage Responses. Antioxid Redox Signal. 2016; 25(15):805-815. PMC: 5107740. DOI: 10.1089/ars.2016.6691. View

12.

Nyugen J, Agrawal S, Gollapudi S, Gupta S . Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol. 2010; 30(6):806-13. PMC: 2970801. DOI: 10.1007/s10875-010-9448-8. View

13.

Seidler S, Zimmermann H, Bartneck M, Trautwein C, Tacke F . Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol. 2010; 11:30. PMC: 2910032. DOI: 10.1186/1471-2172-11-30. View

14.

van Duin D, Allore H, Mohanty S, Ginter S, Newman F, Belshe R . Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. J Infect Dis. 2007; 195(11):1590-7. DOI: 10.1086/516788. View

15.

Wang Q, Westra J, van der Geest K, Moser J, Bijzet J, Kuiper T . Reduced levels of cytosolic DNA sensor AIM2 are associated with impaired cytokine responses in healthy elderly. Exp Gerontol. 2016; 78:39-46. DOI: 10.1016/j.exger.2016.02.016. View

16.

Pillai P, Molony R, Martinod K, Dong H, Pang I, Tal M . Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science. 2016; 352(6284):463-6. PMC: 5465864. DOI: 10.1126/science.aaf3926. View

17.

Panda A, Qian F, Mohanty S, van Duin D, Newman F, Zhang L . Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010; 184(5):2518-27. PMC: 3867271. DOI: 10.4049/jimmunol.0901022. View

18.

Agrawal A, Tay J, Ton S, Agrawal S, Gupta S . Increased reactivity of dendritic cells from aged subjects to self-antigen, the human DNA. J Immunol. 2009; 182(2):1138-45. PMC: 2621318. DOI: 10.4049/jimmunol.182.2.1138. View

19.

Qian F, Wang X, Zhang L, Lin A, Zhao H, Fikrig E . Impaired interferon signaling in dendritic cells from older donors infected in vitro with West Nile virus. J Infect Dis. 2011; 203(10):1415-24. PMC: 3080893. DOI: 10.1093/infdis/jir048. View

20.

Tseng C, Perrone L, Zhu H, Makino S, Peters C . Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. J Immunol. 2005; 174(12):7977-85. DOI: 10.4049/jimmunol.174.12.7977. View