Published in:
Open Access
01-12-2014 | Research article
Superior antigen-specific CD4+T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older
Authors:
Robert B Couch, José M Bayas, Covadonga Caso, Innocent Nnadi Mbawuike, Concepción Núñez López, Carine Claeys, Mohamed El Idrissi, Caroline Hervé, Béatrice Laupèze, Lidia Oostvogels, Philippe Moris
Published in:
BMC Infectious Diseases
|
Issue 1/2014
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Abstract
Background
The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses.
Methods
This observer-blind study, conducted in the United States (US) and Spain during the 2008–2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in ≥65 year-old adults.
Medically-stable adults aged ≥65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18–40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-γ, or TNF-α, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells.
Results
A total of 192 adults were vaccinated: sixty nine and seventy three ≥65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the ≥65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p < 0.001). On Days 42 and 180, the adjusted-geometric mean specific CD4+ T-cell frequencies were also higher in the TIV/AS03 recipients than in the TIV recipients (p < 0.001). Furthermore, the adjusted-geometric mean specific CD4+ T-cell frequencies were higher in the ≥65 year-old recipients of TIV/AS03 than in the18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011).
Conclusion
This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population.