The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumor-associated self-antigen in aged, immunosenescent mice
Open accessAbstract
BACKGROUND: Ineffective induction of T cell mediated immunity in older individuals remains a persistent challenge for vaccine development. Thus, there is a need for more efficient and sophisticated adjuvants that will complement novel vaccine strategies for the elderly. To this end, we have investigated a previously optimized, combined molecular adjuvant, CASAC (Combined Adjuvant for Synergistic Activation of Cellular immunity), incorporating two complementary Toll-like receptor agonists, CpG and polyI:C, a class-II epitope, and interferon (IFN)-γ in aged mice. FINDINGS: In aged mice with typical features of immunosenescence, antigen specific CD8+ T cell responses were stimulated after serial vaccinations with CASAC or Complete/Incomplete Freund's Adjuvant (CFA/IFA) and a class I epitope, deriving either from ovalbumin (SIINFEKL, SIL) or the melanoma-associated self-antigen, tyrosinase-related protein-2 (SVYDFFVWL, SVL). Pentamer analysis revealed that aged, CASAC/SIL-vaccinated animals had substantially higher frequencies of H-2K(b)/SIL-specific CD8+ T cells compared to the CFA/IFA-vaccinated groups. Similarly, higher frequencies of H-2K(b)/SVL-pentamer+ and IFN-γ+ CD8+ T cells were detected in the aged, CASAC + SVL-vaccinated mice than in their CFA/IFA-vaccinated counterparts. In both antigen settings, CASAC promoted significantly better functional CD8+ T cell activity. CONCLUSION: These studies demonstrate that functional CD8+ T cells, specific for both foreign and tumour-associated self-antigens, can be effectively induced in aged immunosenescent mice using the novel multi-factorial adjuvant CASAC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aged CASAC-vaccinated animals had substantially higher levels of antigen specific CD8+ T cells compared with mice vaccinated with complete/incomplete Freund adjuvant.
“Pentamer analysis revealed that aged, CASAC-vaccinated, animals had substantially higher levels of antigen specific CD8+ T cells compared with mice vaccinated with complete/incomplete Freund adjuvant.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [220]
In aged mice, antigen specific CD8+ T cell responses were stimulated after serial vaccinations with CASAC and a class I epitope.
“Accordingly, in aged mice, antigen specific CD8+ T cell responses were stimulated after serial vaccinations with CASAC and a class I epitope, deriving either from ovalbumin or the melanoma-associated self-antigen, tyrosinase-related protein-2.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [220]
CASAC promoted significantly better functional CD8+ T cell activity.
“Therefore, CASAC promoted significantly better functional CD8+ T cell activity (220).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [220]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fitzgerald, M., Hayward, I. P., Thomas, A. C., Campbell, J. H., & CAMPBELL, G. R. (1995) · Cited by 2,552 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,175 · see citing works
Gavazzi, G., & Krause, K.-H. (2002) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(02)00437-1 · Cited by 990 · see citing works
The aging of the immune system
Weiskopf, D., Weinberger, B., & Grubeck-Loebenstein, B. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00927.x · Cited by 908 · see citing works
Cutting edge: impaired toll-like receptor expression and function in aging
Renshaw, M., Rockwell, J., Engleman, C., Gewirtz, A., Katz, J., & Sambhara, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.4697 · Cited by 626 · see citing works
Challenges for vaccination in the elderly
Aspinall, R., Giudice, G. D., Effros, R. B., Grubeck‐Loebenstein, B., & Sambhara, S. R. (2007) · Immunity & Ageing · doi:10.1186/1742-4933-4-9 · Cited by 205 · see citing works
Goldinger, S. M., Dummer, R., Baumgaertner, P., Mihic‐Probst, D., Schwarz, K., Hammann‐Haenni, A., Willers, J., Geldhof, C., Prior, J. O., Kündig, T. M., et al. (2012) · European Journal of Immunology · doi:10.1002/eji.201142361 · Cited by 201 · see citing works
KLRG1—more than a marker for T cell senescence
Henson, S. M., & Akbar, A. N. (2009) · AGE · doi:10.1007/s11357-009-9100-9 · Cited by 191 · see citing works
Zhu, Q., Egelston, C. A., Aravindhan, V., Uematsu, S., Akira, S., Klinman, D. M., Belyakov, I. M., & Berzofsky, J. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805325105 · Cited by 183 · see citing works
T-cell immunosenescence: lessons learned from mouse models of aging
Maue, A. C., Yager, E. J., Swain, S. L., Woodland, D. L., Blackman, M. A., & Haynes, L. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.04.007 · Cited by 182 · see citing works
Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo
Haynes, L., Eaton, S. M., Burns, E. M., Rincon, M., & Swain, S. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.9.5194 · Cited by 162 · see citing works
Mifsud, E. J., Tan, A. C. L., & Jackson, D. C. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00079 · Cited by 160 · see citing works
Decman, V., Laidlaw, B. J., Doering, T. A., Leng, J., Ertl, H. C. J., Goldstein, D. R., & Wherry, E. J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101098 · Cited by 132 · see citing works
Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy
Escors, D. (2014) · New Journal of Science · doi:10.1155/2014/734515 · Cited by 114 · see citing works
Moody, M. A., Santra, S., Vandergrift, N., Sutherland, L. L., Gurley, T. C., Drinker, M. S., Allen, A. A., Xia, S.-M., Meyerhoff, R. R., Parks, R., et al. (2014) · Journal of Virology · doi:10.1128/jvi.03309-13 · Cited by 90 · see citing works
Tarhini, A. A., Butterfield, L. H., Shuai, Y., Gooding, W. E., Kaliński, P., & Kirkwood, J. M. (2012) · Journal of Immunotherapy · doi:10.1097/cji.0b013e318272569b · Cited by 62 · see citing works
Park, H., Adamson, L., Ha, T., Mullen, K., Hagen, S. I., Nogueron, A., Sylwester, A. W., Axthelm, M. K., Legasse, A., Piatak, M., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202958 · Cited by 58 · see citing works
Wells, J. W., Cowled, C. J., Farzaneh, F., & Noble, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.5.3422 · Cited by 53 · see citing works
Self-citationDerhovanessian, E., & Pawelec, G. (2012) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2011.00283.x · Cited by 51 · see citing works
CpG oligodeoxinucleotides functions as an effective adjuvant in aged BALB/c mice
Maletto, B. A., Ropolo, A. S., Liscovsky, M. V., Alignani, D., Glocker, T. M., & Pistoresi-Palencia, M. C. (2005) · Clinical Immunology · doi:10.1016/j.clim.2005.08.016 · Cited by 34 · see citing works
Phenotype and functions of conventional dendritic cells are not compromised in aged mice
Tan, S., Cavanagh, L. L., d'Advigor, W., Shackel, N. A., Groth, B. F. D. S., & Weninger, W. (2012) · Immunology and Cell Biology · doi:10.1038/icb.2011.104 · Cited by 32 · see citing works
A reduced peripheral blood CD4+ lymphocyte proportion is a consistent ageing phenotype
Chen, J., Flurkey, K., & Harrison, D. E. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00347-5 · Cited by 30 · see citing works
CpG ODN enhances immunization effects of hepatitis B vaccine in aged mice.
Qin, W., Jiang, J., Chen, Q., Yang, N., Wang, Y., Wei, X., & Ou, R. (2004) · PubMed · Cited by 28 · see citing works
Immunity, cancer and aging: lessons from mouse models.
Myers, C. E., Mirza, N. N., & Lustgarten, J. (2011) · Europe PMC (PubMed Central) · Cited by 26 · see citing works
Hulseberg, P. D., Zozulya, A. L., Chu, H., Triccas, J. A., Fábry, Z., & Sándor, M. (2009) · Immunology Letters · doi:10.1016/j.imlet.2009.12.004 · Cited by 12 · see citing works
Gravekamp, C., & Chandra, D. (2013) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2013010588 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C. M., Ligotti, M. E., Zareian, N., & Accardi, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02247 · Cited by 693 · see citing works
Self-citationWilson, D. S., Damo, M., Hirosue, S., Raczy, M. M., Brünggel, K., Diaceri, G., Quaglia-Thermes, X., & Hubbell, J. A. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0424-1 · Cited by 71 · see citing works
Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions
Duggal, N. A. (2018) · Biogerontology · doi:10.1007/s10522-018-9771-7 · Cited by 53 · see citing works
Aiello, A., Ligotti, M. E., Garnica, M., Accardi, G., Calabrò, A., Pojero, F., Arasanz, H., Bocanegra, A., Blanco, E., Chocarro, L., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179880 · Cited by 36 · see citing works
Self-citationCostarelli, L., Giacconi, R., Malavolta, M., Basso, A., Piacenza, F., DeMartiis, M., Giannandrea, E., Renieri, C., Busco, F., Galeazzi, R., et al. (2014) · AGE · doi:10.1007/s11357-014-9656-x · Cited by 19 · see citing works
Triggering of Toll-like Receptors in Old Individuals. Relevance for Vaccination
Zareian, N., Aprile, S., Cristaldi, L., Ligotti, M. E., Vasto, S., & Farzaneh, F. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191111155800 · Cited by 10 · see citing works
Self-citationLew, M. H., Norazmi, M. N., & Tye, G. J. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.10.023 · Cited by 9 · see citing works
Self-citationZareian, N., Eremin, O., Pandha, H., Baird, R. D., Kwatra, V., Funingana, I.-G., Verma, C., Choy, D., Hargreaves, S., Moghimi, P., et al. (2024) · Experimental Biology and Medicine · doi:10.3389/ebm.2024.10021 · Cited by 5 · see citing works
Self-citationLew, M. H., Norazmi, M. N., Nordin, F., & Tye, G. J. (2022) · Immunobiology · doi:10.1016/j.imbio.2022.152201 · Cited by 4 · see citing works
Self-citationVaccination in old age: Challenges and promises
Caruso, C., Aiello, A., Pawelec, G., & Ligotti, M. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822569-1.00020-2 · Cited by 4 · see citing works
(2021) · Frontiers research topics · doi:10.3389/978-2-88966-718-5 · Cited by 3 · see citing works
Immune Stimulation of RAP domain binding protein (rTgRA15) from Toxoplasma gondii
Lew, M. H., Noordin, R., Khan, M. M. A., & Tye, G. J. (2018) · Pathogens and Global Health · doi:10.1080/20477724.2018.1536854 · Cited by 1 · see citing works
Self-citation
- Authors
- Tye, G. J., Ioannou, K., Amofah, E., Quartey-Papafio, R., Westrop, S. J., Krishnamurthy, P., Noble, A., Harrison, P. M., Gaensler, K. M. L., Barber, L. D., & Farzaneh, F.
- Affiliations
- Universiti Sains Malaysia (MY)
- King's College London (GB)
- Guy's Hospital (GB)
- University of California, San Francisco (US)
- Corresponding author
- Barber, Linda D.
- Farzaneh, Farzin
- ORCID
- Venue
- Immunity & Ageing
- Published
- 2015-06-25
- Volume
- 12
- Issue
- 1
- Pages
- 6-6
- ISSN
- 1742-4933 (ISSN-L)
- PMC
- PMC4495856
- OpenAlex
- W1584813087
- Cited by
- 12
- References
- 26
- Citations by year
- 2024: 1 · 2022: 2 · 2021: 2 · 2019: 4 · 2018: 2 · 2014: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Immunity & Ageing (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research
- King's College London
- Biotechnology and Biological Sciences Research Council (BB/K013785/1, BB/E005896/1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- immunosenescence, CD8+ T cell responses, tyrosinase-related protein 2, CpG, poly(I:C), interferon-gamma, melanoma vaccine, aged mice, T cell immunity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
