Abstract
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This is not the first time that there have been problems with the flu vaccine. So why do we have so much trouble with this familiar vaccine? The problem is that the flu virus changes its shape every year by processes referred to as antigenic drift (small changes) and antigenic shift (large changes). Therefore, the vaccine (which works by recognizing the viruses shape) has to be regularly reformulated to keep up with the changing nature of the virus. Although the process is reasonably effective, the nature of the virus is such that despite the best guesses of scientists, a suboptimal vaccine results. Moreover, the problem is compounded by the fact that most of the vaccine is manufactured by growing vaccine strains of the virus in fertilized chicken eggs. This is a rather archaic process that is slow and frequently problematic, as was the case for this year's vaccine. Scientists across the globe agree that the solution to the flu vaccine problem is the development of a “universal flu vaccine” that would work by attacking conserved regions of the virus shape that do not change as the virus undergoes seasonal antigenic drift and shift. Such conserved regions of the virus have been identified, but tend to be difficult to access for protective antibodies. Moreover, a successful universal vaccine will probably need to elicit both antibody and T cell responses against multiple conserved antigens. Once developed, such a vaccine (1) would be effective regardless of the nature of the virus encountered, (2) would not necessarily have to be given every year, and (3) could be stockpiled well in advance of seasonal flu epidemics. Although substantial progress is being made in this area, we are still a long way from this important goal.
The problems associated with influenza and influenza vaccines are addressed by two articles in the March issue of Viral Immunology that focused on vaccines in general (Anti-Viral Vaccines: Successes and Prospects, edited by Julia Hurwitz (volume 31, issue 2). Both articles are from leading researchers in the influenza vaccine field. An article by Altman, Angeletti, and Yewdell offers an extensive discussion of the factors that regulate and contribute to antigenic drift in the influenza virus (Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift). The authors point out that antigenic drift is based on the accumulation of amino acid substitutions in viral glycoproteins that gradually alter their antigenicity. This drift is driven primarily through the selection of viruses that are resistant to neutralizing factors, including altered viral binding to host cell receptors.
A major complication with a flu infection is that it sets the scene for dangerous bacterial pathogens to invade the lungs. These include infections by Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenza. A second article by Smith and Huber in the special vaccines issue (The Unexpected Impact of Vaccines on Secondary Bacterial Infections Following Influenza) addresses the impact of vaccines on these secondary bacterial infections. The authors point out that vaccines against bacterial pathogens can reduce coinfection incidence and severity, but few vaccines are available, and tend to have low efficacy. In this context, their article reviews the current knowledge of viral and bacterial vaccines in limiting influenza-associated bacterial infections.
Influenza virus research has come a long way since the horrendous 1918 pandemic. But we still have a long way to go. In the words of Dr. Ed Marcuse, The pandemic influenza clock is ticking. We just don't know what time it is. As important research in this area moves forward, the Viral Immunology Journal will continue to publish groundbreaking research and review articles on the biology of this dangerous pathogen.