H1N1 Vaccine: The Differences Make All the Difference

by:  Natasha Hochlowski
Institution:  Princeton University
Date:  March 2010

This past summer, researchers at Rice University published a paper that could revolutionize the way in which vaccines are manufactured, assisting thousands of people during the current H1N1 virus crisis. Rice Professor of Biochemical and Genetic Engineering Michael Deem came up with a new way of making vaccines, which may be applicable to researchers creating a vaccine for H1N1 "swine" flu. This paper was recently published in the journal Protein Engineering, Design, & Selection.

Deem recognized that he needed to study the proteins in various flu strains,viruses mutate, or randomly change, whenever there are alterations in the protein sequence, because that sequence determines the functioning of the viruses. In his research, Deem compares sequences of amino acids,the building blocks of proteins,in two different strains of H1N1. He then notes the number of differences between the sequences in order to evaluate the possibility of creating a vaccine from one of the strains. A vaccine works by introducing weakened versions of a virus into the body, so that a person's immune system can become accustomed to the virus. Thus, the fewer differences there are between strains, the greater the possibility that one of the strains can be engineered into a vaccine against the other strain. Deem is one of the only researchers to develop such a method: by identifying strains that are very similar, the vaccine will be much easier to engineer, and it will be produced quicker and work more effectively.

Deem's process is useful because of flu viruses' propensity to mutate, which is a problem for manufacturing flu vaccines. In Influenza A, the most prevalent strain of the flu, there are 5 or 6 proteins that can mutate randomly in many different ways. According to Deem, "The virus mutates quite a bit. Normally, when we're doing rational drug design, we're trying to do it against a target protein that is not changing, and we're trying to find something that fits very nicely in the pocket of that protein." In the case of the flu, certain proteins will evolve and change, so that, by the time a vaccine is ready to be administered, it may have become obsolete.

Deem's work involves measuring the differences between the epitopes,the parts of the viruses that are recognized by a person's immune system,in different flu strains. Says Deem, "For the flu, these epitopes change. So rational drug design against one strain of the flu virus would only be useful for that one year, and then the virus would mutate the next year." Deem analyzes the differences by assigning a number to the antigenic distance, a measurement of differences, between two strains. For example, assume that two similar strains are the colors blue and blue-green. The body will recognize the blue-green as being similar to the blue, so they may each be assigned a number of 1,meaning few differences. But if an orange virus is introduced, there are very few similarities between that and the blue, so that may be assigned a number of 50. By analyzing these values, researchers can easily identify which viruses will make good vaccines, and which strains they will be able to combat with those vaccines.

Deem, along with fellow researcher Keyao Pan, is trying to reduce the amount of time between analysis of flu strains and vaccine manufacture and evaluate the effectiveness of potential vaccines. If their methods prove successful, vaccines will be able to be produced as close to flu season as possible, thus reducing the possibility that the virus will mutate before the vaccine can be administered. With our current scientific knowledge, flu vaccines are not highly effective, and are rendered nearly obsolete during times of epidemic, such as the H1N1 "swine" flu. However, with the application of Deem's research, we may be able to create vaccines that are highly effective. We will therefore be able to reduce the risk from the everyday flu and perhaps be able to lower the threat of, or even eliminate, influenza epidemics such as "swine" flu.