Monday, September 30, 2013

T-cells Found To Be Linked To Influenza Immunity – Could A Universal Vaccine Be On The Way?

Influenza, or more commonly referred to as the flu, is a highly contagious virus that affects the respiratory system. Because it is so contagious, it can affect thousands of people annually. In fact, somewhere between 5% and 20% of the United States population will contract the virus each year (2). However, despite its frequency of occurrence, the flu is not always a deadly disease. Of the people who are infected, there is an average of 200,000 hospital visits a year, and, depending on the strain, the number of flu-related deaths can range from 3,000 to 49,000 (2). The following fact is what makes the flu so dangerous though: the virus mutates every year. Every year doctors scramble to create a vaccine that will protect the public from the different flu strains that hit during flu season; they do not always make the appropriate vaccine, though, and that is when fatalities can accumulate. This leads to a pandemic.

The most recent influenza pandemic was the H1N1 virus that occurred in 2009. Also known as swine flu, this virus hospitalized thousands; everyone was caught off guard. On top of that, scientists found that symptoms varied drastically among similar individuals with the swine flu. Some people experienced no symptoms while some were hospitalized. This has shown with the other strains of influenza as well, and this was a question that scientists desperately were trying to find an answer to: What decides whether one is going to be asymptomatic? After the onset of the swine flu in 2009, a group of researchers at Imperial College London began a study hoping to answer this question, and the results that they found were groundbreaking.

In the experiment, Ajit Lalvani and his colleagues recruited 342 participants and followed them during the course of the second H1N1 outbreak in the 2010-2011 season. If they contracted the virus and were originally seronegative for H1N1 antibodies, they were to fill out symptom surveys. This allowed Lalvani and his colleagues to look at these individuals at a molecular level to figure out immunological sources for the different viral responses. They obtained their results by measuring the frequencies of crossreactive T-cells in relation to illness severity as well as symptom severity. They also correlated levels of CD8­+IFN-γ+IL-2- cells (a type of CD8 T cell), and symptom severity. Essentially, they were looking at and quantifying the pre-existing T cell responses to the H1N1 virus compared to the conserved core protein epitopes, as they were researching the possibility of protective ability within T cells and its application to pandemic influenza.

In their results, they found that higher frequencies of the certain type of crossreactive T cell (CD8­+IFN-γ+IL-2-) were related to fewer and less severe flu symptoms and decreased or no viral shedding. Similarly, they found that T cell responses to the conserved CD8 epitopes from three different immune-dominant core proteins (PB1, M1, NP) also corresponded with reduced symptoms and severity. Consequently, from these findings the researchers hypothesized that cellular heterosubtypic immunity may be the reason for the symptomatic differences in those with H1N1. They also theorized that the heterosubtypic immunity may alleviate the serious effects of other disease-inducing viruses. Thus, the amount of certain CD8 T-cells is indirectly correlated to illness severity.

Despite these results, it should be acknowledged that there were several limitations and flaws to this experiment that may or may not affect the conclusions that were made. First of all, the study was done during the second wave of H1N1 virus and not the first due to waiting for ethical approval. The consequences of performing the experiment after the initial H1N1 wave were that the sample size decreased and the confidence intervals increased. However, they still found their data consistent albeit smaller across the board. Lalvani and his colleagues also realized that they could not compare the normally healthy individuals they studied to high risk individuals, but there is a chance the data would still be similar. They also did not measure the role of systemic innate immune responses, only the role of cellular immune responses.

Still, based on these studies, scientists could potentially create a universal flu vaccine for the public. In fact, Lalvani himself said that researchers already know how to stimulate CD8 T-cell creation via vaccine, so it is likely that scientists are now currently using the findings in this paper and experimenting to create a universal vaccine (3). The result of those studies, if successful, could then decrease flu-induced hospital visits and possibly eliminate fatalities (3). It would also be cost-effective, for a lot of money goes into flu vaccine production each year, considering the flu virus mutates every season. Lastly, with a universal vaccine, other viral diseases could attract even more attention. More resources could go to finding universal vaccines for other viruses, which in turn will help millions. These findings are the first step towards a new kind of medicine, and we can only wait and anticipate the medical breakthroughs that doctors, scientists, and researchers will have in the future.

Primary Source:

1.     1..  Sridhar, Saranya et. al. Cellular Immune Correlates of Protection Against Symptomatic Pandemic
Influenza. 22 September 2013. Nature Medicine. Online Publication.

Other Sources: 

2.Flu Information:

3. Interview with Ajit Lalvani/ Quick Information about Paper:


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