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: 2.6). 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: MF59 is an oil-in-water (o/w) emulsion, pre-pared with a low content of the biodegradable oil, squalene (4.3% w/w), which is a naturally occur-ring substance normally found in plants and ani-mals including humans. In humans, squalene is an intermediate in the steroid hormone biosyn-thetic pathway and is a direct synthetic precursor to cholesterol. A normal human is estimated to produce in excess of 1 g of squalene per day, while the amount of squalene contained in the licensed MF59-adjuvanted seasonal influ-enza vaccine is approximately 10 mg per dose. In comparison, the normal dietary intake of squalene in humans is 50–200 mg/day, depend-ing on diet. MF59 is a well-established, safe and potent vaccine adjuvant that has been licensed in more than 20 countries, for more than 13 years for use in an influenza vaccine focused on elderly subjects (Fluad ® , Novartis, Cambridge, MA, USA). During the 2009 H1N1 influenza pandemic, two MF59-adjuvanted vaccines were licensed and used safely in all age groups (down to 6 months of age) including pregnant women. Furthermore, MF59 has been shown to be safe in a seasonal influenza vaccine in infants and children and increased vaccine efficacy from 43 to 89% [1–3]. The overall safety profile of MF59 has been clinically established with a large safety database (>40,000 subjects) and through an extensive pharmacovigilance evalu-ation in excess of 60 million doses distributed commercially as Fluad ® . In addition, approxi-mately 100 million doses of H1N1 pandemic vaccines (Focetria ® and Celtura ® , Novartis) were distributed. The MF59 adjuvant significantly enhances the immunogenicity of influenza vaccines in the elderly, who typically respond poorly to traditional influenza vaccines, owing to age-related impairment of their immune sys-tems (immuno senescence) [4]. Moving beyond seasonal influenza vaccines, MF59 has also been shown to significantly improve the immunoge-nicity of pandemic influenza vaccines and has enabled vaccines with a relatively low antigen content to achieve titers expected to offer pro-tection, and with fewer doses [5–7]. Moreover, the addition of MF59 to the vaccine allows for greater cross-reactivity against viral strains not actually included in the vaccine (Figures 1–4) [6,8]. This is a key attribute, since it is difficult to pre-dict exactly which strain might emerge and cause a pandemic. Following the emergence of the H1N1 pandemic in 2009, an MF59-adjuvanted influenza vaccine received approval for licensure
  • [Show abstract] [Hide abstract]
    ABSTRACT: Influenza pandemic preparedness involves priming of the population with pre-pandemic vaccines. Such vaccines should be well tolerated and induce a long-lasting immunological memory that can effectively be boosted with a single dose of pandemic vaccine once available. The presented studies assessed different prime-boost regimens with a Vero cell-derived whole virus non-adjuvanted H5N1 vaccine. In one study, 281 healthy adult (18-59 years) and 280 elderly (≥60 years) subjects received two vaccinations, 21 days apart, with Vero cell-derived whole virus non-adjuvanted H5N1 vaccine (7.5μg HA antigen A/Vietnam/1203/2004) followed by a 6, 12-15, or 24 month booster (7.5 or 3.75μg A/Indonesia/05/2005 or A/Vietnam/1203/2004). In the other study, 230 healthy adults (18-59 years) received single dose priming (7.5μg A/Vietnam/1203/2004) followed by a 12 month booster (7.5 or 3.75μg A/Indonesia/05/2005). Antibody responses were assessed by microneutralization (MN) and single radial hemolysis (SRH) assay. Vaccine safety was assessed throughout. Two dose priming was equally immunogenic in adults and the elderly: >72% of subjects in each population achieved MN titers ≥1:20 after the second vaccination. Booster vaccinations at 6, 12-15, and 24 months induced substantial antibody increases to both strains: after a 7.5μg A/Indonesia/05/2005 booster, 93-95% of adults and 72-84% of the elderly achieved MN titers≥1:20 against this strain. Homologous and heterologous booster responses were higher in the 7.5μg dose group than in the 3.75μg dose group. Booster responses following single dose priming were similar; a 7.5μg booster dose induced homologous MN titers ≥1:20 in 93% of subjects. A Vero cell derived whole virus non-adjuvanted H5N1 influenza vaccine is well tolerated and induces long-lasting cross-clade immunological memory that can be effectively boosted 1-2 years after two dose or single dose priming, supporting its suitability for pre-pandemic vaccination.
    Vaccine 08/2012; 30(43):6127-35. · 3.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: MF59 is a well-established, safe and potent vaccine adjuvant that has been licensed for more than 13 years for use in an influenza vaccine focused on elderly subjects (Fluad®), Novartis, Cambridge, MA, USA). Recently, MF59 was shown to be safe in a seasonal influenza vaccine for young children and was able to increase vaccine efficacy from 43 to 89%. A key and consistent feature of MF59 is the ability of the emulsion to induce fast priming of influenza antigen-specific CD4(+) T-cell responses, to induce strong and long-lasting memory T- and B-cell responses and to broaden the immune response beyond the influenza strains actually included in the vaccine. The enhanced breadth of response is valuable in the seasonal setting, but is particularly valuable in a (pre-) pandemic setting, when it is difficult to predict which strain will emerge to cause the pandemic. We have shown that the ability of MF59 to increase the breadth of immune response against influenza vaccines is mainly due to the spreading of the repertoire of the B-cell epitopes recognized on the hemagglutinin and neuraminidase of the influenza virus.
    Expert Review of Vaccines 04/2011; 10(4):447-62. · 4.22 Impact Factor


Available from
May 20, 2014