Abstract
Vaccination against influenza is the most effective way to protect the population. Current vaccines provide protection by stimulating functional B- and T-cell responses; however, they are poorly immunogenic in particular segments of the population and need to be reformulated almost every year due to the genetic instability of the virus. Next-generation influenza vaccines should be designed to induce cross-reactivity, confer protection against pandemic outbreaks, and promote long-lasting immune responses among individuals at higher risk of infection. Multiple strategies are being developed for the induction of broad functional humoral immunity, including the use of adjuvants, heterologous prime-boost strategies, and epitope-based antigen design. The basic approach is to mimic natural responses to influenza virus infection by promoting cross-reactive neutralizing antibodies that directly prevent the infection. This review provides an overview of the mechanisms underlying humoral responses to influenza vaccination or natural infection, and discusses promising strategies to control influenza virus.
Highlights
Influenza virus alone causes over 40,000 deaths every year in the United States, and even more during pandemics, like in 2009 with pandemic A/California/07/09 H1N1 virus strain [1, 2]
Antigenic drift represents the principal immune evasion mechanism of influenza virus and has two major consequences: first, the humoral immunity developed in response to previous infections/vaccinations is usually nonfully effective against the new emerging strains, and second, manufacturers need to update the vaccine every year with increasing costs and risks of delays in the release of the lots
We summarize the mechanisms eliciting humoral responses against influenza infection or vaccination, and discuss the approaches that are today under evaluation to develop broadly protective and, hopefully, universal vaccines against influenza
Summary
Influenza virus alone causes over 40,000 deaths every year in the United States, and even more during pandemics, like in 2009 with pandemic A/California/07/09 H1N1 virus strain [1, 2]. Existing vaccines confer acceptable levels of protection in the general population, they are suboptimal, and are associated with some important limitations: (i) antigen composition needs to be updated every year in order to match the new seasonal circulating viruses, (ii) mismatch between the vaccine and the circulating virus can always happen, and (iii) people with a reduced ability to mount an immune response, infants, the elderly, and pregnant women respond suboptimally to these vaccines, requiring a tailored vaccine formulations [7,8,9,10,11]. Antigenic drift represents the principal immune evasion mechanism of influenza virus and has two major consequences: first, the humoral immunity developed in response to previous infections/vaccinations is usually nonfully effective against the new emerging strains, and second, manufacturers need to update the vaccine every year with increasing costs and risks of delays in the release of the lots. We summarize the mechanisms eliciting humoral responses against influenza infection or vaccination, and discuss the approaches that are today under evaluation to develop broadly protective and, hopefully, universal vaccines against influenza
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