![]() So instead of overcoming the problem of antigenic change of the target virus by clever antigen and/or vaccine design, our most successful approach to date has been to develop a system that can rapidly respond to the virus change itself. The World Health Organization (WHO)-led tracking system traces the evolution of these viruses through epidemic seasons and selects the most appropriate virus antigens to be included in the seasonal influenza vaccine.Ĭoncomitant with the development of the WHO tracking system has been the development of a regulatory framework that allows for antigen changes within the context of an approved vaccine process. While influenza B viruses are not further categorized into subtypes, two genetically and antigenically distinct lineages of virus, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, are also found in humans ( 81). Two subtypes, classified based on the antigenic properties of their surface glycoproteins HA and neuraminidase (NA), of influenza A viruses currently circulate in humans, A(H1N1) and A(H3N2). Instead of driving different vaccination approaches, the obstacle of antigen diversity has historically driven the development of a truly remarkable system of global virus tracking and annual vaccine reformulations to ensure vaccine/virus matching.īoth influenza A and B viruses, two genera of the Orthomyxoviridae family, are causes of substantial morbidity and mortality in humans and are targets for our current influenza vaccines. ![]() The inactivated influenza vaccines that are the mainstay of our current influenza vaccination programs generate a relatively narrow immune response that is short-lived. ![]() Unfortunately, this flipside has proved to be a formidable obstacle to overcome. As such, the virus can evolve to evade immunity generated by prior vaccination, and the targeting of HA using conventional approaches provides little hope for substantive improvements in how we vaccinate. The flipside of this conundrum is that the HA globular head is the most variable part of the virus. While other forms of immunity, both humoral and cellular, have been shown to be protective, the HA head-specific antibodies interfere with the attachment of viruses to their cellular surface receptors and are solely capable of neutralizing infection ( 11, 16, 20–22, 45, 51, 91, 92, 102).Ĭurrent influenza vaccine production is based on this understanding, and vaccines are routinely designed to elicit protective neutralizing antibody responses. From a purely immunologic standpoint, it is clear what form of immunity has the most protective ability, which is antibody to the globular head of the viral surface protein hemagglutinin (HA). I nfluenza virus produces a conundrum when it comes to successful vaccination. In this study, we review the problems associated with the changing nature of the virus, and highlight some of the approaches being employed to improve influenza vaccines. It is clear that transformative change of influenza vaccines requires a rethink of how we immunize. Although influenza virus infection induces long-lived immunologic memory to the same or similar strains, most people do not encounter the same strain repeatedly in their lifespan, suggesting that enhancement of natural immunity is required to improve influenza vaccines. Few vaccine production systems have been developed that can entertain such constant changes. This has forced frequent updates of vaccine antigens to ensure that the somewhat narrowly focused vaccine-induced immune responses defend against circulating strains. Influenza viruses undergo antigenic evolution through antigenic drift and shift in their surface glycoproteins. The challenge of vaccinating against influenza lies in the constantly changing nature of the virus itself. However, nearly 70 years of influenza vaccine usage have passed without substantial changes in the underlying principles of the vaccine. Numerous modern technological and scientific advances have changed the vaccine industry.
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