ReviewThe virosome concept for influenza vaccines
Section snippets
Key messages
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Despite the established efficacy of current inactivated influenza vaccines, there is an urgent need for improved flu vaccine formulations.
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In the face of pandemic threat, new influenza vaccines need to induce robust virus-neutralizing antibody responses in immunologically naïve individuals.
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Declining T cell functions with age require that new vaccines for the elderly not only induce solid antibody responses but also stimulate cell-mediated immunity.
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Virosomes are reconstituted influenza virus
Background
Influenza continues to affect thousands of people each year causing epidemics with severe morbidity and considerable excess mortality, the latter particularly among the elderly [1], [2], [3]. Outbreaks are also associated with high economic costs to society [4], [5]. Furthermore, there is increasing concern about a potential new influenza pandemic, since highly pathogenic avian influenza viruses, such as the H5N1 virus currently circulating in South-East Asia, have the ability to cross the
Background
Virosomes represent a novel vaccine presentation form that closely mimics the native virus. Virosomes are virus-like particles, consisting of reconstituted viral envelopes, lacking the viral genetic material. They are generated from virus by a detergent solubilization and reconstitution procedure [40], [41], as discussed in more detail below. Virosomes may be produced from a variety of enveloped viruses, including influenza virus, the resulting particles being similar to the original virus in
Interaction of virosomes with B lymphocytes and antigen-presenting cells
Fig. 5 depicts schematically how virosomes probably interact with cells of the immune system, in particular B lymphocytes and dendritic cells. Haemagglutinin and neuraminidase spikes protruding from the virosomal membrane, as well as foreign antigens that may be coupled to the surface of the virosomes (see below), can be recognized by membrane-associated immunoglobulin receptor molecules on B lymphocytes [56]. The repetitive arrangement of the antigens on the virosomal surface presumably
Antibody responses to influenza
Virosomal influenza vaccines have been extensively investigated in humans. In fact, a virosomal influenza vaccine has been commercially available for a number of years (Inflexal V®, Berna Biotech, Berne, Switzerland). Clinical studies have demonstrated that intramuscular administration of this virosomal influenza vaccine to humans induces haemagglutination-inhibition (HI) titres at least similar to those induced by conventional whole virus or subunit vaccines [64], [65]. Another virosomal
Background
As indicated above, CTLs are responsible for the destruction of virus-infected cells and thus for the clearance of virus infections [58]. In humans, influenza-specific CTLs are mainly directed against epitopes derived from internal proteins of the virus, such as the matrix protein and the nucleoprotein, while in mice immunodominant epitopes are found predominantly on the nucleoprotein [76]. However, other viral antigens including haemagglutinin may also induce biologically relevant CTL
Background
Adjuvants are substances that enhance the immune response. Some adjuvants, like the commonly used aluminium salts or mineral oil serve to form a physical depot retaining the antigen for presentation to cells of the immune system. While stimulating antibody responses, aluminium adjuvants do not effectively augment CTL responses. More sophisticated adjuvants are recognized by receptors on antigen-presenting cells. Engaging of these receptors results in intracellular signalling and in the
Concluding remarks
The suboptimal efficacy of current inactivated influenza vaccines in elderly people as well as the threat of a new influenza pandemic underline the urgent need for more efficacious inactivated flu vaccine formulations. The requirements for such novel vaccines are, however, somewhat divergent. While improvements of vaccines for the elderly are sought primarily at the level of cell-mediated immunity, the most important requirement for pandemic vaccines involves the ability to induce a robust
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