Homologous and heterologous antibody responses to a one-year booster dose of an MF59 (R) Adjuvanted A/H5N1 pre-pandemic influenza vaccine in pediatric subjects

University of Tampere Medical School
Human Vaccines & Immunotherapeutics (Impact Factor: 2.37). 07/2012; 8(7):921-8. DOI: 10.4161/hv.20248
Source: PubMed


Background: Primary immunization with two doses of MF59 (®) -adjuvanted A/H5N1 influenza vaccine has been shown to be highly immunogenic and well tolerated in children and adolescents. Assessment of long-term antibody persistence after priming, and the effects of a one-year booster dose in children and adolescents was needed. Objectives This study assessed homologous and heterologous antibody responses to a one-year booster dose of MF59-adjuvanted A/H5N1 influenza vaccine in previously primed children. Subjects and methods: Twelve months after primary vaccination, toddlers, children and adolescents received a single booster dose of the same A/H5N1 vaccine. Paired sera were collected before and three weeks after booster vaccination. Homologous antibody responses against the A/Vietnam/1194/2004 vaccine strain were measured by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN) assays. Heterologous antibody responses against A/Indonesia/5/2005 and A/Anhui/1/2005 strains were assessed by MN assay only. Results: Twelve months after primary vaccination, persistent, homologous, seroprotective HI antibody titers (≥ 40) were observed in 46%, 26% and 30% of toddlers, children and adolescents; following booster vaccination, seroprotection rates increased to 99%, 98% and 91%, respectively. All toddlers and children, and 99% of adolescents achieved MN antibody titers ≥ 40. Cross-reactive A/H5N1 antibodies were detected in 94-98% of subjects after booster vaccination. Conclusions Two priming doses of MF59-adjuvanted A/H5N1 vaccine resulted in homologous and heterologous antibody responses which persisted for up to one year after immunization. A one-year booster dose was highly immunogenic, generating high homologous and cross-reactive A/H5N1 antibody titers.

1 Follower
14 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Aflunov is an egg-derived, subunit vaccine from Novartis Vaccines and Diagnostics containing 7.5 μg of hemagglutinin (HA) from the avian A/H5N1 virus and the oil-in-water adjuvant MF59. Areas covered: Aflunov behaves as a pre-pandemic vaccine. It has a good safety profile at all ages. At all ages, it induces high and persisting antibody titers and activation of HA-specific Th0/Th1 CD4(+) T cells, the levels of which correlate with the neutralizing antibody titers after a booster dose 6 months later. Aflunov triggers strong immunological memory, which persists for at least 6 - 8 years and can be rapidly boosted with a heterovariant vaccine strain, inducing very high neutralizing antibody titers within one week. These antibodies broadly and strongly cross-react with drifted H5N1 virus strains from various clades. Finally, the MF59 changes the pattern of HA recognition by antibodies that react with the HA1 more than with the HA2 region. Expert opinion: The available data show that Aflunov is a pre-pandemic vaccine suitable not only for stockpiling in case of a pandemic, but also before a pandemic is declared, with the ultimate objective of preventing the onset of an influenza pandemic.
    Expert opinion on biological therapy 11/2012; 13(1). DOI:10.1517/14712598.2013.748030 · 3.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Children are highly vulnerable to infection with novel influenza viruses. It is essential to develop candidate pandemic influenza vaccines which are safe and effective in the pediatric population.Methods. Infants and children aged 6-35 months and 3-8 years were randomized to receive two immunizations with a 7.5 µg or 3.75 µg hemagglutinin (HA) dose of a non-adjuvanted whole-virus A/Vietnam strain H5N1 vaccine; adolescents aged 9-17 years received a 7.5 µg dose only. A subset of participants received a booster immunization with an A/Indonesia strain H5N1 vaccine approximately one year later. HA and neuraminidase antibody responses were assessed.Results. Vaccination was safe and well-tolerated; adverse reactions were transient and predominantly mild. Two immunizations with the 7.5 µg dose of A/Vietnam vaccine induced virus neutralization (MN) titers ≥1:20 against the A/Vietnam strain in 68.8% to 85.4% of participants in the different age groups. After the booster, 93.1% to 100% of participants achieved MN titers ≥1:20 against the A/Vietnam and A/Indonesia strains. NA-inhibiting antibodies were induced in ≥90% of participants after two immunizations with the 7.5 µg A/Vietnam vaccine and in 100% of participants after the booster.Conclusions. A whole-virus H5N1 vaccine is suitable for pre-pandemic or pandemic immunization in a pediatric population.Clinical Trial Registration.
    The Journal of Infectious Diseases 09/2013; 209(1). DOI:10.1093/infdis/jit498 · 6.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The threat of an outbreak of avian-origin influenza H7N9 and the devastating consequences that a pandemic could have on global population health and economies has mobilized programs of constant surveillance and the implementation of preemptive plans. Central to these plans is the production of prepandemic vaccines that can be rapidly deployed to minimize disease severity and deaths resulting from such an occurrence. In this article, we review current H7N9 vaccine strategies in place and the available technologies and options that can help accelerate vaccine production and increase dose-sparing capabilities to provide enough vaccines to cover the population. We also present possible means of reducing disease impact during the critical period after an outbreak occurs before a strain matched vaccine becomes available and consider the use of existing stockpiles and seed strains of phylogenetically related subtypes, alternate vaccination regimes and vaccine forms that induce cross-reactive immunity.
    Expert Review of Vaccines 07/2014; 13(11). DOI:10.1586/14760584.2014.938641 · 4.21 Impact Factor
Show more


14 Reads
Available from