Abstract
Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine.
Highlights
250,000–500,000 deaths are caused by influenza epidemics worldwide yearly, and the death number may be up to millions in a possible influenza pandemic [1,2,3]
These results suggested that extensive challenge studies of protective efficacy against different viruses should be performed to evaluate M2e-based influenza universal vaccines
By attaching a tetramerization sequence and transmembrane/cytoplasmic domains to M2e and expressing the resulting construct in insect cells, we found that M2e can be presented as tetramers, the natural structure of M2e in the virion, on the surfaces of influenza M1
Summary
250,000–500,000 deaths are caused by influenza epidemics worldwide yearly, and the death number may be up to millions in a possible influenza pandemic [1,2,3]. Current influenza vaccines are effective in battling closely matched viruses, major limitations are the need to produce new vaccines every season, the uncertainty in choice of the correct strains, a slow production process requiring embryonated eggs, as well as the inability to prevent an influenza pandemic or the emergence of a new drift strain. Driven by the selective pressure of human immunity, the HA gene undergoes frequent genetic mutation leading to the emergence of new virulent strains [8,9] For these reasons, the seasonal influenza vaccine has to be reformulated annually based on prediction of the upcoming circulating subtypes. Compared to the traditional inactivated or attenuated influenza virus vaccines, new generations of influenza vaccine employ technologic advances aimed at inducing broad cross protection and enhanced immunogenicity These advances include rational design of antigens, integrated adjuvant strategies, more efficient delivery platforms and controlled release technology.
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