Rising Cases of New Bird Flu Highlight Vaccination Debate and Need for New Vaccines

Each year, plenty of people ask the question, “Should I get a influenza vaccination?” For many of those people, the answer is already defined and it is “Too bad, you’re getting one.” Some states, such as New Jersey, have made flu shots mandatory. In Jersey, children 6 months to 5 years old must be vaccinated in order to attend a licensed daycare, preschool or pre-kindergarten, in spite of protest when the law was enacted in 2008. On a different front, hundreds of hospitals across the U.S. have mandated flu shots for employees, under the contention that it improves patient safety. Again, there was turmoil created, including seven workers at Indiana University Health Goshen Hospital being relieved of their jobs for refusing to roll up their sleeves. The reasons against the shot are widespread, including religious beliefs, allergies, vegan lifestyle, uncertainty about safety and efficacy and simply freedom of choice, to name a few.

The Centers for Disease Control and Prevention hopes to have 90 percent compliance in inoculations by the health care work force by 2020. The American Nurses Association and National Nurses United, organizations that represent more than 300,000 nurses in the U.S., think the shot should be recommended, but not mandated with unemployment repercussions to non-compliant employees. What that means…get ready for some battles in court.

Now, this isn’t an exercise to debate the finer points of individual liberties versus public responsibility. This is an opinion encouraging due diligence to make an educated decision. There’s plenty of arguments in either case for today’s flu vaccine, with some calling the push a “marketing machine” and others saying it has absolutely no value, while the CDC still maintains its vaccination recommendation. It’s also a realization that one day the flu shot may be mandated nationwide, just as other vaccinations that have stifled once-prominent or deadly diseases like polio, measles and cowpox. In order for that to happen, though, it seems that some significant strides are necessary to effectively fight the ever-mutating influenza viruses.

Why? Well, because today’s treatment is a bit of a crap shoot, with current formulations only having the ability to include three strains of the flu virus. Each year, a think tank of CDC and affiliates evaluate data and take a guess at which three types of flu will infect people in the upcoming flu season. This is out of countless possibilities and surely can’t include new mutations that haven’t surfaced yet. Then they proceed to approve manufacturers. For the 2013 season, the three strains targeted were A/California/7/2009 (H1N1)-like virus, A/Victoria/361/2011 (H3N2)-like virus, and B/Wisconsin/1/2010-like virus.

The six licensed manufacturers and brand names for 2012/2013:

• Afluria, manufactured by CSL Limited (ASX:CSL) (CMXHF);
• Fluarix, manufactured by GlaxoSmithKline (GSK) Biologicals;
• FluLaval, manufactured by ID Biomedical Corporation (acquired by GSK in 2005 for $1.4 billion);
• FluMist, manufactured by MedImmune Vaccines Inc., the biologics arm of AstraZeneca (AZN) acquired in 2007 for $15.2 billion;
• Fluvirin, manufactured by Novartis (NVS) Vaccines and Diagnostics Limited; and
• Fluzone, Fluzone High-Dose and Fluzone Intradermal, manufactured by Sanofi (SNY) Pasteur

Sanofi Pasteur provides about half of the flu vaccines in the U.S. The nation apparently ran low this year. According to CNBC, as of January 4, there were only about 7 million inoculations left out of the 135 million produced for this year’s flu season. Obviously, people are acting upon the CDC’s recommendation (or being told they have to).

Australia is also feeling the surge of people wanting the flu vaccine. A department spokesman for the National Immunisation Program in Australia said on Monday that unprecedented demand for flu shots is causing a shortage of vaccination shots in the country. The organization provides free shots to people most susceptible to the flu. CSL Limited, as the only manufacturer of the flu vaccine in the southern hemisphere, reported on Tuesday that it has restarted production of its flu vaccine to meet demand.

The crux of the potential for future demand and effectiveness of a flu vaccination seems to rest in the ability of a company to develop a “universal” flu shot that can protect against more than the three strains comprising today’s treatment or to develop methods to expedite vaccine production.

Through a partnership with Biomedical Advanced Research and Development Authority (BARDA), Novartis, in a collaborative effort with Synthetic Genomics Vaccines Inc., has made huge strides in genetic code processes to replicate new viruses and quickly develop a vaccine.

Don’t think vaccines can’t potentially carry serious side effects. A lot was made of Glaxo’s Pandemrix, a monovalent 2009 H1N1 flu vaccine that was used in Europe during the 2009/2010 flu season. Apropos, Pandemrix was never approved in the U.S. and was never used again overseas. The UK Health Protection Agency discovered evidence earlier this year that the vaccine, which includes an adjuvant to stimulate the immune system’s response to the vaccine, was linked to narcolepsy in children.

New processes could be blazing the trail to next-generation vaccines.

In January, the FDA approved Flublok, the first trivalent flu vaccine made using an insect virus expression system and recombinant DNA technology. Developed by privately-held Protein Sciences Corp, Flublok was approved for seasonal flu therapy in people 18 to 49 years of age. The vaccine is made by putting hemagglutinin, a protein from the flu virus, into a virus that infects insect cells, then culturing the cells to grow the protein. Clinical data showed Flublok to be about 45 percent effective against all flu strains, not just three like today’s standard vaccine.

Flublok could be the transition to the next wave of flu vaccines as the technology does not include growing the virus in chicken eggs, as is done in current vaccines, not only expediting manufacturing time, but also making the vaccine available to vegans who don’t want any part of an animal in their body as well as those people with egg allergies. Using cell cultures, rather than eggs could cut production time from about six months down to about eight weeks.

Interestingly, institutional investors in Protein Sciences include Johnson & Johnson (JNJ) and Pfizer, Inc. (PFE).
Overseas, Lothar Stitz of Friedrich-Loeffler Institut in Germany and colleagues are using messenger RNA, a molecule that tells cells which proteins to make, to develop new flu vaccines with promising data to date through in vivo research.

In the States, Madison, Wisconsin-based Flu-Gen is readying to start clinical trials on its REDEE FLU vaccine that infects the nasal canal with a live virus (rather then dead ones like current approved vaccines), priming the immune system. The company has a goal to maneuver down the regulatory pathway to commercialization by 2019.

U.S. World News and Report said last week, “It’s time to worry about the new Chinese bird flu,” in an article discussing the latest developments of the H7N9 virus now infecting more than 100 people, including 22 deaths, and spreading outside of China to Taiwan. The article states that the new version of flu is “very, very unsettling” as a new mixture of three different types of bird flu variants that has been spreading in chickens unnoticed.

Blue Bell, Pennsylania-based Inovio Pharmaceuticals, Inc. (INO) is mentioned in the article for its plans to test the new strain in a controlled lab environment. The company is developing its SynCon vaccine as a new means to create a universal seasonal flu vaccine protecting against known flu strains like H1N1, H3N2, Type B flu strains, subtypes and more as well as new, unmatched strains. Inovio has partnered with Merck & Co. (MRK), the U.S. military, National Institute of Health and more leading names in the health care/biotechnology space in the development of its vaccines. The company is developing vaccines for a variety of diseases, including cervical dysplasia, HIV, hepatitis C, malaria and leukemia, but for the intent of this article, influenza, using a DNA-based vaccine platform that is made in pure water.

Much like the advancements made by Flublok and others aforementioned firms to think outside the box, Inovio’s platform provides scalability, a broader therapeutic and far faster manufacturing than current methods. The company delivered positive interim data in December from an ongoing H1N1 Phase I clinical trial in elderly patients (>65 years of age) with additional data expected later this quarter or early in Q3. In vivo laboratory tests are also being conducted of vaccine constructs for A/H3N2 and Type B influenza.

Whether an advocate or an opponent of influenza vaccinations, the fact is that they are a growing part of the world in varying degrees. Some overseas countries aren’t jumping on the flu vaccination bandwagon, but it certainly doesn’t look like the U.S. government or U.S. organizations are going to wane from their leading roles supporting or mandating vaccinations. From an investors’ standpoint, the majors above have a stronghold on global sales at the moment, but some technologies look to be coming down the pipeline that could provide an opportunity for either a junior to get a boon in value or one of those majors to develop new vaccines or to make an acquisition to potentially grab more of the market.

From a humanitarian standpoint, one can only hope that the mutating strains of influenza can be addressed with new therapies, whether through egg-based methods, cell cultures or genetic engineering to provide a more rapid response vaccine(s).