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

作者：Couch Robert B; Bayas Jose M; Caso Covadonga; Mbawuike Innocent Nnadi^*; Nunez Lopez Concepcion; Claeys Carine; El Idrissi Mohamed; Herve Caroline; Laupeze Beatrice; Oostvogels Lidia; Moris Philippe

来源：BMC Infectious Diseases, 2014, 14(1): 425.

DOI：10.1186/1471-2334-14-425

• Influenza vaccination
• AS03 adjuvant system
• T-cell response
• Elderly
• Immunosenescence
• Cell-mediated immunity

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-gamma, or TNF-alpha, 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.

• 出版日期2014-7-30