The emergence of SARS-CoV-2 variants necessitates ongoing evaluation of vaccine performance. This study evaluates and compares the safety and immunogenicity of the Comirnaty and Spikevax monovalent XBB.1.5 COVID-19 vaccines in an elderly population.

Altogether, 129 elderly individuals were recruited between 2 January and 3 February 2024, and received a booster dose of either Comirnaty (n=59) or Spikevax (n=70) monovalent XBB.1.5 COVID-19 vaccine. Blood samples were collected at before and one month after vaccination. Immunogenicity was assessed by measuring the percentage of IFNγ⁺CD4⁺ and IFNγ⁺CD8⁺ T cells, and neutralizing antibody titers (NT50) using a surrogate virus neutralization test (sVNT). Adverse reactions were recorded and analyzed.

Both vaccines significantly increased the percentage of IFNγ⁺CD8⁺ T cells against XBB.1.5 and wild-type (WT) SARS-CoV-2 at one-month post-vaccination. Spikevax induced a significantly higher percentages of IFNγ⁺CD8⁺ and CD4⁺ T cells against XBB.1.5 than Comirnaty (p<0.001). The proportion of participants showing a positive T cell response to XBB1.5 after vaccination was higher in the Spikevax group (64.3% CD8, 71.4% CD4) than in the Comirnaty group (42.4% CD8, 57.6% CD4). Spikevax also elicited higher NT50 levels against XBB1.5, JN.1 and the latest variant KP.2 than Comirnaty (XBB1.5: p<0.01; KP.2: p<0.05). Fever was more common in the Spikevax group (fever: p=0.006). However, all side effects were short-term and resolved on their own.

Both vaccines induce neutralizing antibody to XBB1.5, JN.1 and KP.2. Specifically, Spikevax induces higher cellular and humoral immune responses than Comirnaty in the elderly, but it is also associated with a higher incidence of fever. These findings can guide public health strategies for vaccinating the elderly population.