Article

A Heterologous MF59-Adjuvanted H5N1 Prepandemic Influenza Booster Vaccine Induces a Robust, Cross-Reactive Immune Response in Adults and the Elderly

Novartis Vaccines and Diagnostics, Via Fiorentina, 1, 53100 Siena, Italy.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.47). 11/2010; 17(11):1817-9. DOI: 10.1128/CVI.00461-09
Source: PubMed

ABSTRACT

Immunogenicity and safety of a booster dose of an MF59-adjuvanted H5N1 vaccine containing 7.5 μg A/turkey/Turkey/1/2005-like (clade 2.2) H5N1 hemagglutinin, given approximately 18 months after primary vaccination with a heterologous strain, were evaluated. The booster vaccine was well tolerated and induced a robust, cross-reactive immune response.

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    • "Vesikari et al. demonstrated the enhanced immunogenicity of MF59 adjuvanted trivalent influenza vaccine in young children [2]. In addition, use of MF59 with avian influenza viruses (H5N1) also showed enhancement of the immune response in adults including the elderly [3]. In the United States, the only approved adjuvants for use in vaccines are aluminum hydroxide, aluminum phosphate, potassium aluminum sulfate (alum) and AS04, which contains both alum and monophosphoryl lipid A [4], [5]. "
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    ABSTRACT: Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.
    Full-text · Article · Jul 2012 · PLoS ONE
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    • "MF59 has been shown to significantly enhance the immunogenicity of influenza vaccines in older adults, resulting in higher antibody titers than conventional unadjuvanted vaccines [225] [226] [227]. Additionally, the antibody responses induced by MF59-adjuvanted vaccine demonstrate broader cross-reactivity with influenza strains not included in the vaccine, potentially offering improved protection in the event of vaccine mismatch with currently circulating strains [228] [229]. In studies performed in mice and humans, MF59 has been shown to enhance the number of influenza specific CD4 T cells and memory B cells [230] [231] [232]. "
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    ABSTRACT: Influenza is an important contributor to morbidity and mortality worldwide. Accumulation of genetic mutations termed antigenic drift, allows influenza viruses to inflict yearly epidemics that may result in 250,000 to 500,000 deaths annually. Over 90% of influenza-related deaths occur in the older adult population. This is at least in part a result of increasing dysregulation of the immune system with age, termed immunosenescence. This dysregulation results in reduced capacity to cope with infections and decreased responsiveness to vaccination. The older adult population is in dire need of improved vaccines capable of eliciting protective responses in the face of a waning immune system. This review focuses on the status of immunity, responses to influenza vaccination, and strategies that are currently being explored to elicit enhanced immune responses in this high risk population.
    Full-text · Article · Feb 2012 · Aging and Disease
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    • "MF59 has been shown to significantly enhance the immunogenicity of influenza vaccines in older adults, resulting in higher antibody titers than conventional unadjuvanted vaccines [225] [226] [227]. Additionally, the antibody responses induced by MF59-adjuvanted vaccine demonstrate broader cross-reactivity with influenza strains not included in the vaccine, potentially offering improved protection in the event of vaccine mismatch with currently circulating strains [228] [229]. In studies performed in mice and humans, MF59 has been shown to enhance the number of influenza specific CD4 T cells and memory B cells [230] [231] [232]. "
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    ABSTRACT: Aging is associated with a decline in immune function (immunosenescence) that leads to progressive deterioration in both innate and adaptive immune functions. These changes contribute to the subsequent increased risk for infectious diseases and their sequelae. Vaccination is the most effective and inexpensive public health strategy for prevention of infection, despite the decreased efficacy of vaccines in older adults due to immunosenescence. The rapid rise in the older adult population globally represents a great challenge for vaccination programs. This article first addresses the status of innate and adaptive immune functions in aging and then focuses on influenza vaccine. The development history of influenza vaccines, current status, and potential strategies to improve the immunogenicity and vaccine effectiveness in older adults are discussed.
    Full-text · Article · Nov 2011 · Expert Review of Vaccines
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