This evidence synthesis has been compiled by members of the CITF Secretariat and does not necessarily represent the views of all CITF members.

By: Varun C. Anipindi

The mRNA-based Pfizer vaccine has demonstrated remarkable efficacy and is approved for use across a wide range of age groups from children aged 12 and up to the elderly. While the specific correlates of protection are still under investigation, an accelerated study published in Nature1 attempts to evaluate the broad range of immune responses elicited after one or two doses of the Pfizer vaccine in individuals ranging from 20 to over 80 years old.

Key points:

  • In a cohort of 140 individuals, scientists observed an inverse relationship between age and neutralizing antibody responses, with a sharp decline observed in individuals aged 80 and up.
  • At least two doses of the Pfizer vaccine were essential for inducing neutralizing antibody responses in individuals aged 80 and up.
  • IFN-g and IL-2 T cell responses were lower in vaccinated individuals aged 80 and up compared to the younger individuals.

Neutralizing antibodies may play a critical role in determining vaccine efficacy, particularly against emerging variants of concern (VOCs). In this study, scientists first investigated the impact of age on viral neutralization following vaccination with the Pfizer vaccine. After the first dose, sera from older adults (>80yo) were remarkably less effective at neutralizing SARS-CoV-2 compared to sera from those <80yo. These neutralization titers improved after the second vaccine dose, with a 12-week interval between doses being better than a 3-week interval. Furthermore, at least two doses were required for neutralizing VOCs such as the Alpha, Beta and Gamma variants. When comparing absolute antibody levels, researchers observed that total IgG and IgG subclasses against the spike protein were also lower in those >80yo compared to the younger group.

Since T cells may also play an important role in limiting disease progression, researchers examined T cell responses post-vaccination by measuring IFN-γ and IL-2 production. Consistent with the antibody responses, there was a negative correlation between age and spike-specific IFN-γ T cell responses, with a sharp decline after the age of 80. A similar but less drastic effect was observed with IL-2 T cell responses. Additionally, the majority of the IFN-γ and IL-2 was produced by CD4+ T cells and not CD8+ T cells within the PBMC samples showing that CD4+ T cells may be the primary cytokine-producing T cells that respond to SARS-CoV-2 antigens after vaccination. Interestingly, unlike antibody levels, spike-specific IFN-γ and IL-2 responses after the first vaccine dose did not significantly increase after the second dose was administered.

Overall, this study indicates that individuals over the age of 80 may induce lower antibody and T cell responses post-vaccination, and as a result, are likely at greater risk for breakthrough infections with VOCs, especially after being partially vaccinated with one dose of the vaccine. While the durability of these responses for long-term protection remains unclear, completing the full vaccination regimen appeared to enhance antibody responses and provide better protection against VOCs, even in the elderly population.


Collier, D.A., Ferreira, I.A.T.M., Kotagiri, P. et al. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature (2021).