Available Vaccines
Immunosenescence: What It Is, Why It Matters, How Vaccination Helps
Definition and Biological Mechanisms
Immunosenescence refers to a gradual decline in immune function with increasing age. The biological mechanisms associated with this include thymic involution with reduced naïve T cells, expansion of late-differentiated or exhausted T cells, impaired B-cell class switching and affinity maturation, diminished NK or neutrophil function, and a chronic low-grade inflammatory state (“inflammaging”). Together, these changes blunt responses to new pathogens and vaccines while increasing baseline inflammation and multimorbidity.
Clinical Consequences
Immunosenescence increases the risk and severity of respiratory infections (e.g., influenza, pneumococcus, RSV, COVID-19), reactivation of latent infections (e.g., herpes zoster), and certain complications (e.g., secondary bacterial pneumonia, cardiovascular events following respiratory infections). It also contributes to reduced vaccine immunogenicity and faster waning.
Malaysia and the Region: Why This Is Urgent
Malaysia is ageing. The proportion of people ≥65 years rose from 4.0% (2000) to 7.2% (2022) and is projected to keep rising through 2030–2040; several states already have ≥7% of their population aged ≥65 years. This demographic shift will expand the proportion of individuals biologically susceptible to immunosenescence and its consequences.
Vaccine Responsiveness in the Context of Immunosenescence
Because of impaired innate sensing, T-helper cell and B-cell function, conventional vaccines can elicit lower peak titres and shorter durability in older adults. Strategies that partly overcome this include:
- Higher antigen dose (e.g., high-dose inactivated influenza vaccine).
- Adjuvanted formulations that recruit innate pathways (e.g., MF59-adjuvanted influenza vaccines; AS01B-adjuvanted RZV).
- Conjugate technology for polysaccharides (e.g., PCV15/PCV20), which drives T-cell–dependent memory.
Randomised and real-world studies show that high-dose/adjuvanted influenza vaccines reduce influenza-related outcomes in older adults compared with standard-dose vaccines, and that modern pneumococcal conjugate vaccines are immunogenic and effective in older adults.
Implications for the Malaysian Adult Immunisation Guidelines
- Prioritise older adults (≥60–65 years) and those with multimorbidity, frailty, or immunocompromising conditions, who experience the most pronounced effects of immunosenescence.
- Influenza: recommend annual vaccination, with preference for enhanced formulations (high-dose or adjuvanted) where available and affordable, given their superior protection in older adults and Malaysia’s demonstrated burden.
- Pneumococcal: adopt conjugate-based schedules for adults age ≥65 and for younger adults with risk conditions, with consideration of sequential strategies depending on product availability and evolving evidence. Malaysian mortality data in seniors argue for proactive uptake.
- Herpes zoster: recommend RZV (2 doses) for adults age ≥50 (including immunocompromised where allowed), given sustained efficacy and regional burden projections that include Malaysia.
- Additional doses: continue COVID-19 vaccination programmes, Td/Tdap every 10 years, and hepatitis B catch-up for non-immune risk groups.
- Implementation levers: increase access and uptake (through public funding for priority groups, integration into chronic disease clinics, pharmacy vaccination, and seasonal campaigns) to counter historically low adult vaccine coverage in the region.
References
- Aw, D., Silva, A. B., & Palmer, D. B. (2007). Immunosenescence: emerging challenges for an ageing population. Immunology, 120(4), 435–446. https://doi.org/10.1111/j.1365-2567.2007.02555.x
- Montgomery, R. R., & Shaw, A. C. (2015). Paradoxical changes in innate immunity in aging: recent progress and new directions. Journal of Leukocyte Biology, 98(6), 937–943. https://doi.org/10.1189/jlb.5MR0315-104R
- Mad Tahir, N. S., Ismail, A., Aljunid, S. M., Abdul Aziz, A. F., Azzeri, A., & Alkhodary, A. A. (2023). Estimating the economic burden of influenza on the older population in Malaysia. PloS one, 18(11), e0294260. https://doi.org/10.1371/journal.pone.0294260
- Sundaramurthy, S. S. R., Allen, K. E., Fletcher, M. A., Liew, K. F., Borhanuddin, B., Ali, M., Morales, G., Gessner, B., Naidoo, J., & Southern, J. (2024). Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013-2015). BMC infectious diseases, 24(1), 79. https://doi.org/10.1186/s12879-023-08611-3
- Han, R., San Martin, P., Ahmed, N., Guzman-Holst, A., Mohy, A., Pinto, T., de Veras, B., Gomez, J. A., Bibera, G. L., & van Oorschot, D. A. M. (2024). Modelling the Public Health Burden of Herpes Zoster and the Impact of Adjuvanted Recombinant Zoster Vaccine in Five Selected Countries in Southeast Asia. Infectious Diseases and Therapy, 13(4), 761–778. https://doi.org/10.1007/s40121-024-00945-y
- Doherty, T. M., Connolly, M. P., Del Giudice, G., Flamaing, J., Goronzy, J. J., Grubeck-Loebenstein, B., Lambert, P. H., Maggi, S., McElhaney, J. E., Nagai, H., Schaffner, W., Schmidt-Ott, R., Walsh, E., & Di Pasquale, A. (2018). Vaccination programs for older adults in an era of demographic change. European Geriatric Medicine, 9(3), 289–300. https://doi.org/10.1007/s41999-018-0040-8