Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine.

Publication Type
Journal Article
Year of Publication
Mbawuike, Innocent N; Atmar, Robert L; Patel, Shital M; Corry, David B; Winokur, Patricia L; Brady, Rebecca C; Chen, Wilbur H; Edwards, Kathryn M; Creech, C Buddy; Walter, Emmanuel B; Frey, Sharon E; Belshe, Robert B; Goll, Johannes B; Hill, Heather; Keitel, Wendy A
Date Published
2016 Jan 20
Adjuvants, Immunologic; Adult; Age Factors; Aged; Cytokines; Female; Granzymes; Humans; Immunity, Cellular; Immunization, Secondary; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Influenza, Human; Interferon-gamma; Leukocytes, Mononuclear; Male; Middle Aged; Vaccines, Inactivated; Young Adult

PURPOSE: The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses.

METHODS: Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus.

RESULTS: PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results.

CONCLUSION: CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine.