Cutting-Edge Approaches Toward Novel and Cross-Protective Influenza Vaccines
The currently available vaccines against influenza are seasonal, viral strain specific, and hence, their efficacy is limited when the circulating strain is not the one included in them. We describe herewith some of the novel approaches for developing infl
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Cutting-Edge Approaches Toward Novel and Cross-Protective Influenza Vaccines Ruth Arnon and Tamar Ben-Yedidia
Abstract
The currently available vaccines against influenza are seasonal, viral strain specific, and hence, their efficacy is limited when the circulating strain is not the one included in them. We describe herewith some of the novel approaches for developing influenza vaccines, in particular peptide- or epitope-based vaccines. A discussion of the epitope-based approach is provided, emphasizing its limitations and advantages, as well as a detailed description of the known influenza epitopes. Finally, we describe our own approach for the design of an epitope-based broad-spectrum “universal” flu vaccine for human use, which is comprised of a synthetic protein expressing multiple copies of nine different conserved epitopes of influenza proteins. These epitopes are common to the vast majority of influenza virus strains regardless of their antigenic drifts and shifts. The vaccine, activating both the humoral and cellular arms of the immune response in both animal models and humans, is presently in phase II clinical trials and is expected to confer cross-strain immunity and to protect also against future strains of the influenza virus.
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Introduction
Influenza is a highly infectious disease caused by frequently mutating influenza viruses. It spreads rapidly around the world in seasonal epidemics, affecting 10–20% of the total population. According to the World Health Organization (WHO), 250,000–500,000 people worldwide die of seasonal influenza annually. Influenza is also associated with pulmonary and cardiovascular complications,
R. Arnon (*) Weizmann Institute of Science, Rehovot, Israel e-mail: [email protected] A. von Gabain and C. Klade (eds.), Development of Novel Vaccines, DOI 10.1007/978-3-7091-0709-6_8, # Springer-Verlag Wien 2012
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leading to high morbidity and mortality rates, affecting mainly at-risk populations such as toddlers, elderly, and individuals with chronic diseases. There are three types of influenza viruses: A, B, and C. Influenza A is responsible for about 80% of influenza disease in humans, influenza B viruses are accountable for additional 20% of influenza infection, and influenza C viruses rarely infect humans. Influenza type A viruses are the most common and are characterized by many substrains and species specificity. They are considered the major cause of widespread seasonal epidemics and pandemics (every 10–30 years) due to the frequent antigenic changes (drifts and shifts) of their surface proteins—hemagglutinin (HA) and neuraminidase (NA). Antigenic drifts are minor changes in the virus that occur continually over time, whereas a major change that happens occasionally is called “antigenic shift.” When shift happens, most people have little or no protection against the new virus. Influenza type A viruses exhibit both kinds of changes, whereas type B viruses and probably those of type C change only by the more gradual process o
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