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

• Published in: BMC infectious diseases 2014-07, Vol.14 (1), p.425-425, Article 425
• Main Authors: Couch, Robert B, Bayas, José M, Caso, Covadonga, Mbawuike, Innocent Nnadi, López, Concepción Núñez, Claeys, Carine, El Idrissi, Mohamed, Hervé, Caroline, Laupèze, Béatrice, Oostvogels, Lidia, Moris, Philippe
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adolescent; Adult; Aged; Analysis; Antibodies, Viral - blood; Assaigs clínics; CD4-Positive T-Lymphocytes - physiology; CD8-Positive T-Lymphocytes - physiology; Clinical trials; Cytomegalovirus; Drug dosages; Female; Grip; Health aspects; Humans; Influenza; Influenza Vaccines - classification; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Lymphocytes; Male; Medicine; Older people; Pandemics; Persones grans; Single-Blind Method; Vaccination; Vaccines; Vacunació; Virology; Writing; Young Adult
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/1471-2334-14-425

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. 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. 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). 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. (Clinicaltrials.gov.). NCT00765076.