With swine flu infections now being reported in six different countries, and concern mounting for even more, researchers are looking for ways to keep the outbreak in check. Influenza's unpredictability has stymied efforts to create a universal vaccine that could be mass-produced in advance of a pandemic threat and used to treat a variety of different virus strains.

Instead, drug companies annually try to predict which strains are most likely to circulate and then make enough of a particular flu vaccine to address those strains. Unfortunately, the wrong type of influenza vaccination provides little protection: for example, vaccination with seasonal influenza vaccine containing human influenza A (H1N1) would not be expected to provide protection against swine influenza A (H1N1) viruses, according to the U.S. Centers for Disease Control. The H and N refer to viral proteins, hemagluttinin and neuraminidase, that help the virus infect cells and reproduce within a host. Even viruses that share the same major subtypes—in this case, the H1 and N1—can have subtler differences and a vaccine against one might not generate antibodies that are effective against the other.

Some researchers say a universal influenza vaccine could be on its way, though. In a recent study of 377 healthy adults receiving three injections of a universal influenza vaccine, known as Bivalent Influenza Peptide Conjugate Vaccine (BIPCV), over a six month period, Saint Louis University Center for Vaccine Development researchers say they found that a low dose of the vaccine evoked an immune response—high antibody titers—similar to levels associated with protecting small animals infected with influenza from serious disease and death. Robert Belshe, the center's director and the lead researcher who studied the vaccine made with proteins from strains of influenza viruses A and B, said in a statement, however, that more research is needed to determine the effectiveness of this approach against a deadly influenza pandemic. Belshe presented his findings earlier this week at the National Foundation for Infectious Disease Conference for Vaccine Research in Baltimore.

The key to creating a universal vaccine is to determine what different influenza strains have in common. Influenza vaccines are affected by virus mutations and the interchange of genes from animal and human strains, known respectively as "drift and shift," according to Belgian molecular biologist Walter Fiers. In an interview last year with ScientificAmerican.com, Fiers noted, "You need a vaccine that is not invalidated by drift and shift." With the universal vaccine doctors could, just like for polio, give an immunization—and then again, a month later, another immunization, and perhaps a year later another one. He added, "You have more possibilities to induce a full-blown immunity." For a universal vaccine to be effective, however, Fiers pointed out that it must be administered nasally because nose drops, unlike flu shots, don't require medical expertise to be administered.

Without an easily delivered nasal or oral vaccine, hospitals worldwide are ill-prepared to manage massive vaccinations. The University of Leicester and University Hospitals of Leicester NHS Trust predict a six-month time lag before effective strain-specific vaccines can be manufactured in the event of a flu pandemic. In a paper published earlier this week in the Proceedings of the National Academy of Sciences of the USA, Iain Stephenson, a consultant in Infectious Diseases at the Leicester Royal Infirmary and a professor at the University of Leicester's Department of Infection, Immunity and Inflammation, makes the case for a pre-pandemic vaccine to mitigate the worst effects of pandemic flu. "If an influenza pandemic occurs, vaccination will be the main way to protect the population," he said in a statement, although he projected in his research that the major current threat seemed to be from avian influenza H5N1 (bird flu).

Another option might be the use of solid metal microneedle arrays, rather than hypodermic needles, coated with inactivated influenza virus for cutaneous influenza vaccine delivery in mice induced strong antibody responses against influenza virus, suppressing hemagglutination activity similar to an intramuscular vaccine injection, according to a team of Emory University and the Georgia Institute of Technology researchers. "These results show that [microneedles] are highly effective as a simple method of vaccine delivery to elicit protective immune responses against virus infection," the researchers conclude in a study published earlier this week in Proceedings of the National Academy of Sciences (PNAS).

Several pharmaceutical companies are responding to the World Health Organization's (WHO) need for help to stem a possible pandemic. Sanofi Pasteur, the vaccines division of France's sanofi-aventis Group, is well-positioned to help, given the company's announcement last month that its pandemic influenza vaccine for human use Emerflu has been granted marketing authorization in Australia by that country's Therapeutic Goods Administration (TGA) in that country. In March, Sanofi-aventis also announced plans to build a $132 million facility to manufacture influenza vaccine in Mexico to be built and operated by sanofi Pasteur.

Researchers from Rockville, Md. drug company Novavax, Inc., along with CDC scientists, published a study last month in which they successfully protected mice against a reconstructed virus from the 1918 Spanish flu outbreak through intranasal immunization with H1N1 virus-like particles (VLPs), The Scientist reported earlier this week. Novavax has two vaccine candidates in clinical trials: One for avian flu that just completed Phase IIa trials, and a seasonal flu vaccine candidate currently in Phase IIa trials.

GlaxoSmithKline says it is working with the WHO, CDC, and U.S. Department of Health and Human Services (HHS) to test a number of potential vaccines, as well as its antiviral treatment Relenza, to help reduce the impact and spread of the new influenza virus. Deerfield, Ill.-based Baxter International Inc. is likewise working with the WHO on a potential vaccine to curb the swine flu virus, the Chicago Tribune reported Monday.

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