Vaccine Effectiveness: Shall I compare thee to getting hit by a car?

Format Video

 

Let’s say when crossing a busy highway on foot without looking you have a 50% chance of getting hit by a car. But if you look before crossing, then you have only a 20% chance of getting hit. By looking, you’ve reduced your risk of getting hit by 60% [(50-20)/(50)=60%]. It’s not perfect, and there’s room to improve, but it’s clearly wiser to look before crossing.

How is Flu Vaccine Effectiveness measured?

The CDC recently announced this past season’s flu vaccine effectiveness was 47% – a marked improvement over last year’s abysmal 23%, and slightly better than the 10-year average of about 40%.

But what exactly does 47% mean? A 47% less chance of getting the flu this past winter if you got the flu shot in the fall? A 47% less chance of dying? Of going to hospital?

And does it measure ‘flu’ in terms of lab-confirmed blood tests? Doctor visits for flu-like illnesses? Or self-reporting (oh man I feel awful…must be the flu!)

Is that 47% effectiveness the same for all people? Healthy, elderly, children?

In fact, the way vaccine effectiveness is measured varies. But for the past 13 years, the CDC has used a “very accurate and sensitive laboratory test” to confirm that a person who has gone to the doctor because of a flu-like illness actually has the flu (and not just something else like a bad cold or similar infection). They then compare between those who have the flu and those who don’t, those who got the flu shot and those who didn’t.

What does Flu Vaccine Effectiveness mean?

How is VE calculated - BiondVaxThere are a few ways of thinking about what vaccine effectiveness (VE) actually means. Let’s take VE=60% as an example. The CDC indicates that a VE of 60% “means that the flu vaccine reduces a person’s risk of developing flu illness that results in a visit to the doctor’s office or urgent care provider by 60%.”

Put another way, a VE=60% indicates a 60% reduction in disease occurrence among a vaccinated group versus an unvaccinated group, or a 60% reduction from the number of cases you would expect if they have not been vaccinated. [Source: CDC]

Flu vs. Car

Returning to our laissez-faire pedestrian, even when looking before crossing, you’re still quite susceptible (20%) to getting hit. What if we added novel technologies, like cross walks, traffic lights, and pedestrian bridges? Along with looking before crossing, the new measures would likely approach 100% effectiveness!

With an average ~40% flu vaccine effectiveness, the NIAID/NIH, the WHO, and CDC are calling for R&D into improved vaccines. There are a number of groups pursuing the goal of “universal” flu vaccines that provide enhanced and broadened protection from the flu.  Each group is exploring different methods (to return to the analogy, some are developing crosswalks, others traffic lights, and others pedestrian bridges). BiondVax, having completed 5 human clinical trials and currently conducting two additional Phase 2 trials, is likely the closest to the finish line. The promising results give hope that within a few years your relatively ineffective annual flu shots will be replaced by an improved flu shot effective for multiple years against all seasonal and pandemic flu viruses.


Notes:
> The numbers I’ve used are just for example. In reality, seasonal flu infects around 5-15% of the unvaccinated population.
> Big thanks to Matan Animation Studios for permission to share their video.
> Further reading:(1) http://www.who.int/influenza/vaccines/virus/recommendations/201502_qanda_vaccineeffectiveness.pdf (2) http://www.cdc.gov/flu/about/qa/vaccineeffect.htm

The Race is on for a Universal Flu Vaccine

For much of the United States, winter means cold weather, snow, sleet and friendly reminders to get flu shots. Indeed, vaccinations remain an important aspect when it comes to combatting a deadly and costly public health issue that causes approximately 23,000 deaths in the United States each year and global loss of life for up to 500,000 people, according to the World Health Organization (WHO).

The impact of influenza is massive. Each year in the USA it infects up to 20 percent of the population and results in 200,000 hospitalizations. Given the magnitude of the problem, some might be surprised to learn the effectiveness of flu vaccinations varies markedly from year to year. For example, vaccine effectiveness was estimated at roughly 20 percent during the 2014-15 flu season, a dire situation that compelled Congress to hold hearings in February and November last year regarding the nation’s preparedness for uncontrolled flu outbreaks.

Last year’s low effectiveness rates for flu vaccinations did have an upside. The public has paid more attention to the scientific community’s quest for an innovative flu vaccine that will lead to lower flu-related mortality and hospitalization rates.

The race is on for better and broader flu vaccines

“Universal” vaccination is a broad term favored by media, but it speaks directly to potential vaccines that may one day broadly protect against all or most strains of flu virus. As reported by Science and Nature Medicine during August, progress is well underway, foreshadowing possible advances that are significantly better than today’s flu vaccination process, which is not only largely ineffective, but also highly inefficient.

The existing seasonal flu vaccination requires six months of lead time to develop the inoculation while relying on production processes that utilize 1940s-era technology. The end product typically does not provide protection against newly appearing ‘pandemic’ strains of the virus, which explains why public health officials were wholly unprepared for the outbreak of Swine Flu back in 2009.

Generally speaking, there are three influenza types known as A, B and C. Type A flu virus is found in human and non-human species and responsible for pandemic outbreaks (avian and swine flu) as well as strains that are behind widely-reported annual flu outbreaks. There are 25 known type A “subtypes” alone. Type B flu is found only in humans and may cause less severe symptoms than type A and do not create pandemics. Type C causes mild, cold-like symptoms.

The flu shots that primary care physicians prescribe each year have very low effectiveness rates for a simple reason. The WHO has to make a prediction about the dominant flu strain far in advance of flu season due to the six-month-long production cycle for vaccinations. Unfortunately, this “educated guess” approach results in frequent discrepancies between the specific flu strains used to manufacture the vaccine and the dominant strains of flu that circulate in any given season. As reported by the CDC, the 2014-15 flu season yielded the lowest flu vaccine effectiveness rate for the general population over the past five years due to a “mismatch” between the flu vaccination and the actual dominant strain.

The challenge for scientists is to move away from the existing estimation model. In addition to being inefficient, these vaccines are based on creation of antibodies that are ineffective against intracellular flu pathogens – microorganisms contained within cells. Antibodies can’t bind to and thereby neutralize the flu virus when it is located inside cells. This scenario accounts for the ineffectiveness of vaccination against a multitude of flu strains that are subject to frequent and unpredictable mutations.

Further, current vaccines are only effective against the virus when located in certain parts of the body, outside of the cells. As a result, the vaccine is ineffective once the virus has invaded the body and moved inside cells. Even if the vaccine happens to be a perfect match for the season’s flu virus, the current vaccine is akin to a boxer sent into the fight with one hand tied behind its back.

Finding a solution is not an easy task

Science’s answer to the challenge posed by the flu virus is the creation of a vaccine that acts against a denominator that is common to every influenza strain. One approach that holds great promise is called “cell-mediated immunity.” This approach stimulates the immune system to activate white blood cells within the human body for the purpose of eradicating different pathogens.

Unlike the current approach of growing antibodies over a period of months, cell-mediated immunity encourages the body to use its own cells in removing infected cells and thereby more efficiently halts the flu virus.

There are several benefits to flu vaccines that utilize the science of cell-mediated immunity. This type of vaccine will induce long-lasting protection. It will be available any time of the year. It will be manufactured on demand with a short-production cycle that is far more efficient than the current six-month process. And it will also target pandemic Type A influenza strains that cannot be conquered by the current vaccination process.

Flu exacts a terrible annual death toll on the world’s human population. Data from the National Institute of Health shows that every year more people receive vaccinations but are not better protected. The silver lining is the scientific community’s response. One day soon, your doctor’s friendly reminder to get a flu shot will come with real assurance that the inoculation will protect most, if not all, people from the dangerous consequences of the flu.

[This article is a reproduction of Dr. Babecoff’s article originally published in The Huffington Post]