Ben Locwin, Contributing Editor11.09.16
We’re now deep into seasonal influenza immunization time, where we seem to be faced with vaccination encouragement signs and posters at nearly every store and pharmacy. Just today I saw 6 such signs beckoning the public to get immunized. Seasonal influenza immunization rates for adults during the last flu season were about 42% (NIS, 2016). But at least in adults, all of the superfluous signage isn’t driving actual behavior changes to any large degree. The current trends for vaccination uptake among adults and children are shown in Figure 1.
It's not all hype, because about 5,000-45,000 deaths recorded in the U.S. every year are associated with influenza.
There have been slight changes to the contraindications for this year’s flu vaccine, specifically that recipients with egg allergies can receive any licensed, recommended age-appropriate influenza vaccine and no longer have to be monitored for 30 minutes after receiving the vaccine. People with severe egg allergies should be vaccinated in a medical setting and be supervised by a health care provider who is able to recognize and manage severe allergic conditions. (cf. CDC).
What does social media have to do with the flu vaccine?
There has been more interest coming from the public about non-egg-based vaccines, principally those made with cell culture. This avoids the risk of egg allergies entirely. However, human behavior and the power of social media are difficult forces to overcome. I would suggest that it’s not only whether or not we can successfully transition all or many of our vaccines and candidates to cell culture and RNA inoculations, but whether or not public perception is on the side of accepting them.
We are living in an interesting if not strange time, where the public has been afforded so many benefits of our advanced medical care that people have in some small, and not so small, part begun to refuse and demonize vaccines. In the mid-1950s, the public was so gripped by the fear of pediatric paralysis (polio myelitis) that they could not line up fast enough for their polio vaccines, which as we know produced remarkable successes.
These days there is little of this immense and present threat as we had seen in decades past, so the healthy masses begin to question the value of vaccines since they don’t remember the fear, disability and death that swept the world only several decades ago.
This is a critical piece of understanding for those researching and producing vaccines. Remember, it’s not just orthopraxis (proper conduct of) science that matters, or whether or not we can successfully and safely produce immunizations through newer methods, but what the public perception and uptake will be that will ultimately determine their financial viability in the market and the new vaccines’ ability to create or maintain herd immunity.
Nevertheless, a cell culture-based trivalent flu vaccine called Flucelvax was approved by FDA in 2012 in adults 18 and over, and just this year, a quadrivalent cell culture Flucelvax was approved for people 4 years and older.
A technology and modality in search of diseases?
At many vaccine conferences that I’ve attended and spoken at, there continues to be a mid-level buzz that vaccines are one of those treatments for which there isn’t enough interest to really invest the big bucks needed to truly move the needle. This isn’t necessarily the case, because for example, uptake of Human Papillomavirus vaccines has been brisk, especially in Australia, where The National HPV Vaccination Program began in 2007 for females, and was extended to include males in 2013.
Research studies out of Australia have shown an incredible decrease in rates of high-grade cervical abnormalities since sweeping advocacy for the HPV vaccine was put into effect in 2007. The vaccine in use is protective against the two high-risk HPV types—16 and 18—which cause 70% of cervical cancers in women and 90% of all HPV-related cancers in men. And it’s not just HPV that this is potentially attenuating; HPV is a cofactor in certain forms of skin cancer (squamous cell carcinoma), and Australia at the moment has been presenting with some of the highest rates of skin cancer compared with other regions around the world.
But remember, just having tremendously positive data like this will not sway the public in large part. People like to think that individually they are very rational and make evidence-based decisions, however the reality is very much the opposite. Most times, when confronted with objective evidence and epidemiological data, people defer to emotion and peer groups’ anecdotes to make their decisions on healthcare.
What to do when our backup plan is a nonstarter? FluMist 2016
Back to seasonal influenza. For this year, the 2016/2017 flu season, the Advisory Committee on Immunization Practices (ACIP) has recommended that no one is to use the FluMist nasal flu vaccine. Remember that this vaccine was created primarily to have another offering for disease prevention that was non-injectable, which was more palatable to those who refused on the basis of a needle puncture—it’s the only non-injectable currently on the market. The LAIV (live attenuated influenza vaccine) vaccine was produced in a novel way to allow the influenza virus to replicate in the slightly (a couple of degrees) cooler environment of the nose relative to the body. For this reason, it was designed so that the nasal spray inoculation wouldn’t be able to cause systemic flu, but would elicit an immune reaction to develop antibodies to the antigens.
It’s important to note that the ACIP’s guidance was based on FluMist’s lack of efficacy this year, and not because it poses any adverse safety risks. It’s presumably as safe as ever, it just didn’t demonstrate any efficacy beyond placebo for this particular season. So the risk this year is that pediatric populations and others that would have been immunized with the mist now will not be if the only alternative is the syringe. Much of what the outcome will be that we’re waiting on is how persistent clinics and healthcare facilities are with insisting on patients receive their vaccine. Time will tell, and the CDC publishes vaccine coverage statistics throughout flu season, so we’ll have some data to examine over the next few months.
As far as protective components in this year’s flu vaccine, for the majority of vaccine doses which are used (often trivalent), they contain two A-type strains and one B-type strain: A/California/7/2009 (H1N1)pdm09-like virus; A/Hong Kong/4801/2014 (H3N2)-like virus; and B/Brisbane/60/2008-like virus (B/Victoria lineage).
For the quadrivalent vaccine, a fourth strain is added, another B-type called B/Phuket/3073/2013-like virus (B/Yamagata lineage).
Conclusion
Many innovator companies and contract vendors offer egg-based production of vaccines, efficient and cost-effective methods for producing cell culture vaccines, and hybrid approaches, which continues to allow us to evolve our production strategies to meet new epidemiological challenges we face with a refreshed immunization armamentarium, such as greater numbers of doses for growing populations or expanded age ranges, antigen-sparing strategies, RNA vaccines, etc. But continuing to make sure we produce safe and effective vaccines isn’t enough at the moment—we need to also address the market (i.e., the people) and do our part whenever we can to be advocates for the preservation of health in our communities via vaccines. We’re all part of the solution to this, so make sure to be immunized and encourage those around you to do the same.
References
Ben Locwin
Ben Locwin, PhD, MBA, MS writes the Clinically Speaking column for Contract Pharma and is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He is an expert media contact for the American Association of Pharmaceutical Scientists (AAPS) and a committee member for the American Statistical Association (ASA). He also provides advisement to many organizations and boards for a range of business, healthcare, clinical, and patient concerns. He can be reached at ben.locwin@healthcarescienceadvisors.com.
It's not all hype, because about 5,000-45,000 deaths recorded in the U.S. every year are associated with influenza.
There have been slight changes to the contraindications for this year’s flu vaccine, specifically that recipients with egg allergies can receive any licensed, recommended age-appropriate influenza vaccine and no longer have to be monitored for 30 minutes after receiving the vaccine. People with severe egg allergies should be vaccinated in a medical setting and be supervised by a health care provider who is able to recognize and manage severe allergic conditions. (cf. CDC).
What does social media have to do with the flu vaccine?
There has been more interest coming from the public about non-egg-based vaccines, principally those made with cell culture. This avoids the risk of egg allergies entirely. However, human behavior and the power of social media are difficult forces to overcome. I would suggest that it’s not only whether or not we can successfully transition all or many of our vaccines and candidates to cell culture and RNA inoculations, but whether or not public perception is on the side of accepting them.
We are living in an interesting if not strange time, where the public has been afforded so many benefits of our advanced medical care that people have in some small, and not so small, part begun to refuse and demonize vaccines. In the mid-1950s, the public was so gripped by the fear of pediatric paralysis (polio myelitis) that they could not line up fast enough for their polio vaccines, which as we know produced remarkable successes.
These days there is little of this immense and present threat as we had seen in decades past, so the healthy masses begin to question the value of vaccines since they don’t remember the fear, disability and death that swept the world only several decades ago.
This is a critical piece of understanding for those researching and producing vaccines. Remember, it’s not just orthopraxis (proper conduct of) science that matters, or whether or not we can successfully and safely produce immunizations through newer methods, but what the public perception and uptake will be that will ultimately determine their financial viability in the market and the new vaccines’ ability to create or maintain herd immunity.
Nevertheless, a cell culture-based trivalent flu vaccine called Flucelvax was approved by FDA in 2012 in adults 18 and over, and just this year, a quadrivalent cell culture Flucelvax was approved for people 4 years and older.
A technology and modality in search of diseases?
At many vaccine conferences that I’ve attended and spoken at, there continues to be a mid-level buzz that vaccines are one of those treatments for which there isn’t enough interest to really invest the big bucks needed to truly move the needle. This isn’t necessarily the case, because for example, uptake of Human Papillomavirus vaccines has been brisk, especially in Australia, where The National HPV Vaccination Program began in 2007 for females, and was extended to include males in 2013.
Research studies out of Australia have shown an incredible decrease in rates of high-grade cervical abnormalities since sweeping advocacy for the HPV vaccine was put into effect in 2007. The vaccine in use is protective against the two high-risk HPV types—16 and 18—which cause 70% of cervical cancers in women and 90% of all HPV-related cancers in men. And it’s not just HPV that this is potentially attenuating; HPV is a cofactor in certain forms of skin cancer (squamous cell carcinoma), and Australia at the moment has been presenting with some of the highest rates of skin cancer compared with other regions around the world.
But remember, just having tremendously positive data like this will not sway the public in large part. People like to think that individually they are very rational and make evidence-based decisions, however the reality is very much the opposite. Most times, when confronted with objective evidence and epidemiological data, people defer to emotion and peer groups’ anecdotes to make their decisions on healthcare.
What to do when our backup plan is a nonstarter? FluMist 2016
Back to seasonal influenza. For this year, the 2016/2017 flu season, the Advisory Committee on Immunization Practices (ACIP) has recommended that no one is to use the FluMist nasal flu vaccine. Remember that this vaccine was created primarily to have another offering for disease prevention that was non-injectable, which was more palatable to those who refused on the basis of a needle puncture—it’s the only non-injectable currently on the market. The LAIV (live attenuated influenza vaccine) vaccine was produced in a novel way to allow the influenza virus to replicate in the slightly (a couple of degrees) cooler environment of the nose relative to the body. For this reason, it was designed so that the nasal spray inoculation wouldn’t be able to cause systemic flu, but would elicit an immune reaction to develop antibodies to the antigens.
It’s important to note that the ACIP’s guidance was based on FluMist’s lack of efficacy this year, and not because it poses any adverse safety risks. It’s presumably as safe as ever, it just didn’t demonstrate any efficacy beyond placebo for this particular season. So the risk this year is that pediatric populations and others that would have been immunized with the mist now will not be if the only alternative is the syringe. Much of what the outcome will be that we’re waiting on is how persistent clinics and healthcare facilities are with insisting on patients receive their vaccine. Time will tell, and the CDC publishes vaccine coverage statistics throughout flu season, so we’ll have some data to examine over the next few months.
As far as protective components in this year’s flu vaccine, for the majority of vaccine doses which are used (often trivalent), they contain two A-type strains and one B-type strain: A/California/7/2009 (H1N1)pdm09-like virus; A/Hong Kong/4801/2014 (H3N2)-like virus; and B/Brisbane/60/2008-like virus (B/Victoria lineage).
For the quadrivalent vaccine, a fourth strain is added, another B-type called B/Phuket/3073/2013-like virus (B/Yamagata lineage).
Conclusion
Many innovator companies and contract vendors offer egg-based production of vaccines, efficient and cost-effective methods for producing cell culture vaccines, and hybrid approaches, which continues to allow us to evolve our production strategies to meet new epidemiological challenges we face with a refreshed immunization armamentarium, such as greater numbers of doses for growing populations or expanded age ranges, antigen-sparing strategies, RNA vaccines, etc. But continuing to make sure we produce safe and effective vaccines isn’t enough at the moment—we need to also address the market (i.e., the people) and do our part whenever we can to be advocates for the preservation of health in our communities via vaccines. We’re all part of the solution to this, so make sure to be immunized and encourage those around you to do the same.
References
- Centers for Disease Control and Prevention. (2016). Frequently Asked Flu Questions 2016-2017 Influenza Season. http://www.cdc.gov/flu/about/season/flu-season-2016-2017.htm
- Centers for Disease Control and Prevention. (2016). ACIP votes down the use of LAIV for 2016-2017 flu season. http://www.cdc.gov/media/releases/2016/s0622-laiv-flu.html
- DeBold, T. & Friedman, D. (2015). Battling Infectious Diseases in the 20th Century: The Impact of Vaccines. Wall Street Journal. http://graphics.wsj.com/infectious-diseases-and-vaccines/
- Cancer Council Australia. (2016). HPV vaccine. http://www.hpvvaccine.org.au/Immunise Australia Program. (2016). Human papilloma virus (HPV). http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/content/immunise-hpv
Ben Locwin
Ben Locwin, PhD, MBA, MS writes the Clinically Speaking column for Contract Pharma and is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He is an expert media contact for the American Association of Pharmaceutical Scientists (AAPS) and a committee member for the American Statistical Association (ASA). He also provides advisement to many organizations and boards for a range of business, healthcare, clinical, and patient concerns. He can be reached at ben.locwin@healthcarescienceadvisors.com.