Immunogenicity and Safety of the Influenza A/H1N1 2009 Inactivated Split-Virus Vaccine in Young and Older Adults: MF59-Adjuvanted Vaccine versus Nonadjuvanted Vaccine

Abstract

Since initial reports in April 2009, the pandemic influenza A (H1N1) virus has spread globally. Influenza vaccines are the primary method for the control of influenza and its complications. We conducted a multicenter clinical trial to evaluate the immunogenicity and safety of H1N1 vaccine (Green Cross Co.) in young adults (18 to 64 years) and the elderly (>65 years) using a two-dose regimen, with the doses administered 21 days apart. Three different regimens of hemagglutinin antigen were comparatively analyzed: 3.75 g (MF59 adjuvanted) versus 7.5 g (MF59 adjuvanted) versus 15 g (nonadjuvanted) in young adults and 3.75 g (MF59 adjuvanted) versus 7.5 g (MF59 adjuvanted) in the elderly. In young adults, all three vaccine regimens met the European Agency for the Evaluation of Medicinal Products (EMA) criteria after the first dose. In the elderly, on day 21 after the first dose, the rates of seroprotection and seroconversion were significantly higher for the 7.5-g dose of MF59 adjuvanted vaccine than for the 3.75-g dose (58.0% versus 44.3% [P ‫؍‬ 0.03] and 53.7% versus 37.2% [P < 0.01], respectively). After the second dose, the geometric mean titer (GMT) increment was blunted with a 15-g dose of nonadjuvanted vaccine, whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In conclusion, a single 7.5-g dose of MF59 adjuvanted vaccine would have a practical advantage over a two-dose, 3.75-g, MF59 adjuvanted vaccine priming schedule. Following a two-dose priming schedule, the increase in hemagglutinin inhibition titers was higher with MF59 adjuvanted vaccine than with nonadjuvanted vaccine.

Comparison of the Adverse Events Associated with MF59-Adjuvanted and Non-Adjuvanted H1N1 Vaccines in Healthy Young Male Korean Soldiers

“…Since our study was not a phase III clinical trial using random allocation, such differences in risk factor allocation were expected. Finally, our adverse event results seemed to be lower than in previous reports (11,12). The reason for this difference is that the male soldiers aged 20-25 years were specifically selected as subjects.…”

“…The immunogenicity of the non-adjuvanted vaccine was 76.3z and 78.1z and the adjuvanted vaccine was 66.7z and 78.1z (11).…”

Comparison of the Long-Term Immunogenicity of Two Pandemic Influenza A/H1N1 2009 Vaccines, the MF59-Adjuvanted and Unadjuvanted Vaccines, in Adults

“…In addition, there is a chance that the content (amount and ratio) of hemagglutinin antigen and MF59 adjuvant were not optimal. Based on the results of the clinical trials, the lowest concentration of the MF59-adjuvanted vaccine (3.75 g hemagglutinin antigen and 4.875 mg MF59) was selected as an antigen-sparing strategy in the Republic of Korea during the 2009 and 2010 pandemic seasons (2).…”

Influenza vaccination for older adults

“…The adjuvanted vaccine was also well tolerated without serious adverse events. 40 Thus, in the elderly, a two-dose priming strategy with adjuvanted vaccine appears to be a promising option.…”