T-helper 1 cells elicited by H5N1 vaccination predict seroprotection

Background.Vaccination is the best measure to protect the population against a potential influenza H5N1 pandemic, but 2 doses of vaccine are needed to elicit protective immune responses. An immunological marker for H5N1 vaccine effectiveness is needed for early identification of the best vaccine candidate.Methods.We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with Matrix M. Sixty adult volunteers were vaccinated intramuscularly with 2 doses of either 30μ g hemagglutinin (HA) alone or with 1.5, 7.5, or 30μ g HA and Matrix M adjuvant (50μg). The humoral response was measured by the hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays, and the CD4 ⁺ T-helper 1 (Th1)-cell response was measured by intracellular staining for the cytokines interleukin 2, interferon , and tumor necrosis factor α. Results.The adjuvanted vaccine effectively induced CD4 ⁺ Th1-cell responses, and the frequency of influenza-specific Th1 cells after the first vaccine dose predicted subsequent HI, MN, and SRH seroprotective responses after the second vaccination.Conclusions.These results support early identification of Th1-cell responses as a predictive biomarker for an efficient vaccine response, which could have great implications for early identification of persons with low or no response to vaccine when evaluating future pandemic influenza vaccines.