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

BMC Infectious Diseases

Philippe Moris¹  Lidia Oostvogels⁶  Béatrice Laupèze¹  Caroline Hervé¹  Mohamed El Idrissi⁶  Carine Claeys⁶  Concepción Núñez López²  Innocent Nnadi Mbawuike⁵  Covadonga Caso⁴  José M Bayas³  Robert B Couch⁷ 

[1] GlaxoSmithKline Vaccines, Rixensart, Belgium;Servicio de Prevención Hospital Universitario La Paz, Madrid, Spain;Centro de Vacunación de Adultos, Servicio de Medicina Preventiva y Epidemiología, Hospital Clínic, Barcelona, Spain;Servicio de Prevención de Riesgos Laborales, Hospital Clínico San Carlos, Madrid, Spain;Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, BCM280, Houston, TX 77030, USA;GlaxoSmithKline Vaccines, Wavre, Belgium;Department of Molecular Virology and Microbiology, Baylor College of medicine, Houston, Texas, USA

关键词: Cell-mediated immunity;    Immunosenescence;    Elderly;    T-cell response;    AS03 adjuvant system;    Influenza vaccination;   

Others  :  1127252
DOI  :  10.1186/1471-2334-14-425

 received in 2014-02-22, accepted in 2014-07-15,  发布年份 2014

【 摘 要 】

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.

Trial registration

(Clinicaltrials.gov.). NCT00765076.

【 授权许可】

   
2014 Couch et al.; licensee BioMed Central Ltd.

【 图 表 】

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