Induction of an effective anti-Amyloid-β humoral response in aged mice

Tomer Illouz, Ravit Madar, Tamir Hirsh, Arya Biragyn, Eitan Okun

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Aging-related decline in immune functions, termed immunosenescence, is a primary cause of reduced protective responses to vaccines in the elderly, due to impaired induction of cellular and humoral responses to new antigens (Ag), especially if the response is T cell dependent. The result is a more severe morbidity following infections, more prolonged and frequent hospitalization, and a higher mortality rate than in the general population. Therefore, there is an increasing need to develop vaccination strategies that overcome immunosenescence, especially for aging-related diseases such as Alzheimer's disease (AD). Here we report a new vaccination strategy harnessing memory-based immunity, which is less affected by aging. We found that aged C57BL/6 and 5xFAD mice exhibit a dramatic reduction in anti-Amyloid-β (Aβ) antibody (Ab) production. We aimed to reverse this process by inducing memory response at a young age. To this end, young mice were primed with the vaccine carrier Hepatitis B surface antigen (HBsAg). At an advanced age, these mice were immunized with an Aβ1-11 fused to HBsAg. This vaccination scheme elicited a markedly higher Aβ-specific antibody titer than vaccinating aged unprimed mice with the same construct. Importantly, this vaccine strategy more efficiently reduced cerebral Aβ levels and altered microglial phenotype. Overall, we provide evidence that priming with an exogenous Ag carrier can overcome impaired humoral responses to self-antigens in the elderly, paving the route for a potent immunotherapy to AD.

Original languageEnglish
Pages (from-to)4817-4829
Number of pages13
Issue number34
StatePublished - 9 Aug 2021

Bibliographical note

Funding Information:
This study was conducted in the Paul Feder laboratory of Alzheimer’s disease research and was supported by the Clore Israel Foundation and in part by the Intramural Research Program of the National Institute on Aging, NIH.

Publisher Copyright:
© 2021 Elsevier Ltd


  • Alzheimer's disease
  • Amyloid-β
  • Immunosenescence
  • Microglia
  • Priming
  • Vaccine


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