Dose Of MF59-adjuvanted Vaccine Research Articles

Immunogenicity of low-dose MF59-adjuvanted 2009 influenza A/H1N1 vaccine in dialysis patients

In response to the pandemic 2009 A/H1N1 virus, monovalent MF59-adjuvanted vaccines were prepared. Recently, single 3.75-μg doses of MF59-adjuvanted vaccines have shown good immunogenicity in young adults. However, the immunogenicity of these vaccines has not been evaluated in dialysis patients. Dialysis patients received a single 3.75-μg dose of MF59-adjuvanted vaccine by intramuscular injection. For immunogenicity assays, serum samples were obtained before vaccination and 28 days after vaccination. All sera were tested by hemagglutination inhibition assays. Overall, 48 hemodialysis (HD) patients and 34 peritoneal dialysis (PD) patients were included in immunogenicity analysis. In HD patients, geometric mean titers (GMTs) were significantly increased compared with baseline GMTs in both young (aged 18-60 years) and elderly (aged ≥ 60 years) patients (51.2 ± 51.4 vs. 14.1 ± 20.7 in young patients, P = 0.012; 37.9 ± 73.9 vs. 6.8 ± 8.0 in elderly patients, P = 0.018, respectively). The rates of seroprotection and seroconversion were 27.6 and 17.2 % in young patients and 31.6 and 26.3 % in elderly patients, respectively. Among PD patients, GMTs were increased only in young patients (39.8 ± 51.4 vs. 6.8 ± 5.0, P = 0.001). The rates of seroprotection and seroconversion were 36.0 and 36.0 % in young patients and 11.1 and 0.0 % in elderly patients, respectively. A single 3.75-μg dose of MF59-adjuvanted vaccine was suboptimal to elicit protective antibody response in dialysis patients. Antibody responses against vaccine were compromised especially in elderly PD patients. Trials of different vaccination protocols such as a two-dose schedule or a higher hemagglutinin antigen dose of MF59-adjuvanted vaccine are necessary for improving antibody response in dialysis patients.

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

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 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) versus 15 μg (nonadjuvanted) in young adults and 3.75 μg (MF59 adjuvanted) versus 7.5 μg (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-μg dose of MF59 adjuvanted vaccine than for the 3.75-μg 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-μg dose of nonadjuvanted vaccine, whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In conclusion, a single 7.5-μg dose of MF59 adjuvanted vaccine would have a practical advantage over a two-dose, 3.75-μg, 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.

Assessment of the safety, tolerability and kinetics of the immune response to A/H1N1v vaccine formulations with and without adjuvant in healthy pediatric subjects from 3 through 17 years of age

Background: The recent global A/H1N1v pandemic led to major efforts to develop effective vaccines against the novel virus, while global demand and limited production capacity focused attention on dose sparing and schedules. Methods: An open-label phase III study of immunogenicity and safety of novel A/H1N1v vaccines included 392 Costa Rican children in two pediatric cohorts (3–8 and 9–17 years). They received two doses, of either an MF59®-adjuvanted formulation containing 7.5 μg antigen or non-adjuvanted formulations containing 15 or 30 μg antigen, three weeks apart. Immunogenicity was assessed as hemagglutination inhibition (HI) titers using the CBER licensure criteria. Results: All three vaccines elicited immune responses in 9–17 year-olds meeting CBER criteria three weeks after one dose; responses were not enhanced by second dose. In 3–8 year-olds only the adjuvanted vaccine met the CBER criteria after one dose, but all three vaccines met criteria after second dose. All vaccines were well tolerated; no related Serious Adverse Events (SAE) and few severe solicited reactions were reported. MF59-adjuvanted vaccine was associated with more reports of injection site pain and tenderness and overall systemic solicited reactions, most notably in older subjects, all of which decreased after the second dose. Conclusion: One dose of non-adjuvanted A/H1N1v vaccine is adequate in 9–17 year-olds, but younger children require either one dose of MF59-adjuvanted vaccine or two doses of non-adjuvanted vaccine to achieve protective titers. Enhanced immunogenicity with MF59 is associated with a small increase in reactogenicity, but no safety issues.

Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine

The 2009 pandemic influenza A (H1N1) virus has emerged to cause the first pandemic of the 21st century. Development of effective vaccines is a public health priority. We conducted a single-center study, involving 176 adults, 18 to 50 years of age, to test the monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and nonadjuvanted forms. Subjects were randomly assigned to receive two intramuscular injections of vaccine containing 7.5 microg of hemagglutinin on day 0 in each arm or one injection on day 0 and the other on day 7, 14, or 21; or two 3.75-microg doses of MF59-adjuvanted vaccine, or 7.5 or 15 microg of nonadjuvanted vaccine, administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay and a microneutralization assay on days 0, 14, 21, and 42 after injection of the first dose. The most frequent local and systemic reactions were pain at the injection site and muscle aches, noted in 70% and 42% of subjects, respectively; reactions were more common with the MF59-adjuvanted vaccine than with nonadjuvanted vaccine. Three subjects reported fever, with a temperature of 38 degrees C or higher, after either dose. Antibody titers, expressed as geometric means, were higher at day 21 among subjects who had received one dose of MF59-adjuvanted vaccine than among those who had received one dose of nonadjuvanted vaccine (P<0.001 by the microneutralization assay). By day 21, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 77 to 96% and 92 to 100% of subjects receiving MF59-adjuvanted vaccine, respectively, and in 63 to 72% and 67 to 76% of those receiving nonadjuvanted vaccine, respectively. By day 42, after two doses of vaccine, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 92 to 100% and 100% of recipients of MF59-adjuvanted vaccine, respectively, and in 74 to 79% and 78 to 83% of recipients of nonadjuvanted vaccine, respectively. Monovalent 2009 influenza A (H1N1) MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection after a single dose is administered. (ClinicalTrials.gov number, NCT00943358).