Influenza Vaccines: An Overview for the 2014-2015 Season

It’s that time of year again: the runny nose, sore throat, muscle aches, fatigue, chills, and fever of the 2014-2015 influenza season will soon be in full swing. Although these symptoms may seem benign, the influenza virus has the potential to cause devastating infections. The first, and hopefully final, pandemic of the 21st century occurred during the 2009-2010 influenza season. It is estimated that between 151,700 and 575,400 people worldwide succumbed to the 2009 H1N1 virus during its first year of circulation. Unlike previous pandemics, the 2009 H1N1 virus was fatal in a significant proportion of non-elderly patients. Approximately 80% of H1N1 deaths occurred in people younger than 50 years.^1,2 However, 2009’s H1N1 was nowhere near as deadly as the influenza pandemic of 1918. The “Spanish Flu,” as it was known, exceeded the death toll of World War I, killing an estimated 50 million people.³ Thankfully, increased immunization rates and advancements in epidemiologic forecasting make these catastrophic influenza outbreaks less and less likely, but this progress has not eliminated the virus’ impact on health care.

Influenza is a member of the orthomyxovirus family and comprises 3 basic types: A, B, and C. The virus can be further delineated into subtypes dependent on the glycoprotein surface antigens hemagglutinin (H) and neuraminidase (N). Nomenclature of influenza viruses is described in the following order: virus type, geographic site of origin, strain number, year of isolation, and virus subtype. For instance, one strain of influenza could be described as A/ California/07/2009 (H1N1). Pandemics usually occur when the genetic material of 2 or more of strains combine and create a different combination of surface antigens. This genetic exchange is referred to as an antigenic shift.^4,5 In 1957, an antigenic shift involving a change in viral glycoproteins from H1N1 to H2N2 resulted in a pandemic that caused roughly 70,000 deaths.⁴

Assessing the past 31 influenza seasons, the Centers for Disease Control and Prevention (CDC) found that approximately 80% of influenza infections occurred between January and March. However, the 2 most recent influenza seasons, 2012-2013 and 2013- 2014, were considered outliers in that the peak of these seasons occurred much earlier. While the timing was unusual, most of the viruses identified during these seasons were similar to the familiar vaccine-targeted strains. The predominant circulating influenza subtype of the 2013-2014 season was H1N1. Unlike the aforementioned pandemic of 2009, the 2013-2014 season’s H1N1 affected mostly elderly patients.^6,7

During the 2012-2013 season, the CDC estimated that flu vaccination prevented 79,000 hospitalizations in the United States.⁸ While the constantly changing nature of the influenza virus makes predictions of virulence and activity difficult, vaccination remains the best method of influenza prevention.

Vaccine Recommendations for 2014-2015

Vaccine recommendations for the 2014-2015 influenza season were announced in late August by the CDC Advisory Committee on Immunization Practices. The CDC continues to recommend annual influenza vaccinations for patients 6 months and older. The trivalent and quadrivalent formulations are available and contain the same virus strains as last season. Both formulations include the A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012-like viruses. The quadrivalent formulations incorporate an additional strain, the B/ Brisbane/60/2008-like virus.⁹ No additional guidance or preference in formulations is provided regarding the 2should be used with caution, and the decision should be carefully assessed by the patient’s health care provider. Contraindications to the LAIV can be found in Online Table 2. Those who are not eligible for receipt of the LAIV should be directed to a provider capable of obtaining and administering the inactivated influenza vaccine (IIV) unless the patient has a history of anaphylaxis with previous influenza vaccines.^10-12

Table 2: Contraindications to the Live-attenuated Influenza Vaccine (LAIV)¹²

- Age < 2 years or >49 years of age

- Pregnancy

- Immunocompromise

- History of egg allergy

- Age 2 through 4 years in patients who have asthma or who have had a wheezing episode in past 12 months

- Antiviral medication use in previous 48 hours

New Aspects of the 2014-2015 Recommendations

The primary change to the recommendations for this year relates to the use of the live-attenuated influenza vaccine (LAIV) in children. It is now recommended that intranasal LAIV be administered in children 2 to 8 years of age, as studies demonstrate its increased protection against influenza. It is important to note that the CDC strongly advises against deferring vaccine administration if LAIV is unavailable. Simply put, any vaccine is better than no vaccine. Children 6 months to 8 years of age still require 2 doses of influenza vaccine, given at least 4 weeks apart, if they did not receive at least 2 doses of the seasonal influenza vaccine and at least 1 dose of the pandemic 2009 (H1N1) vaccine previously. LAIV contraindications have also become less stringent when it comes to patients with chronic comorbidities. Instead of strictly advocating against the use of LAIV in these patients, the CDC suggests that LAIV should be used with caution, and the decision should be carefully assessed by the patient’s health care provider. Contraindications to the LAIV can be found in Online Table 2. Those who are not eligible for receipt of the LAIV should be directed to a provider capable of obtaining and administering the inactivated influenza vaccine (IIV) unless the patient has a history of anaphylaxis with previous influenza vaccines.^10-12

Recommendations for Special Populations

Strong efforts should be made to ensure immunization in individuals who are at high risk of developing influenzarelated complications. High-risk persons include children younger than 5 years, adults 65 years or older, pregnant women, and patients with certain chronic comorbidities or weakened immune systems (eg, cardiovascular disease, diabetes, HIV/AIDS, malignancy). Since no vaccines are available for infants younger than 6 months, the only source of influenza antibodies available for these patients is their mother. Consequently, vaccination is strongly recommended for pregnant women, but the LAIV should not be administered (see Online Table 2).¹⁰

Recommendations for the Elderly

High-dose influenza vaccines are available for patients over the age of 64 years. With 4 times the amount of antigen, these vaccines have been shown to provide a stronger immune response. High-dose influenza vaccine was modestly more effective for the prevention of influenza compared with standard dose in a recently published trial that included almost 32,000 adults 65 years and older. Laboratory-confirmed influenza occurred in 1.4% of patients in the high-dose group compared with 1.9% of patients in the standard-dose group (relative efficacy of 24% [95% CI 9.7 - 36.5)]).¹³ While serious adverse events in this particular study appeared to be uncommon, a previous study comparing the immunogenicity of high-dose versus standard-dose influenza vaccine in patients 65 years and older found that mild and moderate local reactions occurred more frequently in patients receiving the high-dose vaccine. 14 Currently, the CDC recommends annual influenza vaccination for all patients 65 years and older, but does not provide a preference of high-dose over standard-dose influenza vaccine.

Recommendations for Patients with Egg Allergies

Another important consideration when choosing the appropriate vaccine is how it was manufactured. Certain allergens are present at various levels in the available vaccine products. The amount of egg protein (ovalbumin) is of particular concern for individuals with egg allergies. There are currently 3 different methods to create influenza vaccines: (1) egg-based, (2) cell-based, and (3) recombinant. The egg-based manufacturing process is the most commonly used method to produce live and inactivated influenza vaccines. Influenza viruses are harbored in fertilized hen’s eggs for several days to allow adequate viral replication. Subsequently, the virus undergoes several other processes, including inactivation (if necessary), purification, and testing. The amount of egg protein can be identified by its ovalbumin content (see Table1^15,16,20-31).

Cell-based manufacturing follows a process similar to that of eggbased manufacturing, but instead of replicating the influenza virus in fertilized eggs, the viruses are cultured in mammalian cells. Usually a very minuscule amount of ovalbumin is found in cell-based influenza vaccines. To date, there is only 1 influenza vaccine that utilizes cell-based manufacturing: Flucelvax.¹⁵

The third method relies on recombinant DNA technology to produce a 100% egg-free vaccine product. The H protein from the influenza virus is extracted and mixed with other portions of another virus. This combination is then grown in insect cells for viral replication. Flublok is the first trivalent influenza vaccine made with recombinant DNA technology.¹⁶ It was approved by the FDA in January 2013 for persons 18 through 49 years of age. Guidance in vaccine selection for patients with an egg allergy is provided by the CDC. Those who are able to consume a lightly cooked egg without experiencing a reaction can receive usual vaccinations, but should be observed for a minimum of 30 minutes after vaccination. Flublok can be administered to patients who experience hives after eating eggs or egg-containing foods, as well as patients who experience more severe reactions after egg consumption including cardiovascular, respiratory, or gastrointestinal symptoms, and patients who have required epinephrine and/or emergency medical attention after egg consumption.^10,17,18

Pharmacist Role in Influenza Immunization

Pharmacists are able to act at the forefront and play an integral role as advocates for influenza prevention. Because of this, it is important for pharmacists to stay up-to-date regarding influenza vaccine recommendations and vaccine availability. Regardless of the health care setting, pharmacists are able to provide helpful patient education concerning the importance of the influenza vaccine and potential complications associated with acute viral illness. At each clinical encounter, pharmacists should assess the need for the influenza vaccine and identify patients at risk for developing influenza-related complications. In the hospital setting, pharmacists can take advantage of opportunities to vaccinate patients prior to discharge. Those who are able to provide vaccinations in outpatient settings are also in a great position to promote influenza immunizations. During the 2013-2014 influenza season, the second-most common place for adults to receive their influenza vaccines was a store or pharmacy.¹⁹ With the rapidly increasing role of pharmacists in immunization and the rising popularity of walk-in outpatient/ ambulatory vaccination, the opportunity for the pharmacist to influence patient immunization rates cannot be overstated. It is important to remember that every patient interaction is a chance to prevent influenza and related complications.

Jacqueline Isip, PharmD, is a PGY-2 infectious diseases pharmacy resident at UNC Health Care. She earned her doctor of pharmacy degree at the University of Michigan.

References

1. Centers for Disease Control and Prevention. First global estimates of 2009 H1N1 pandemic mortality released by CDC-led collaboration. www.cdc.gov/flu/spotlights/pandemic-global-estimates.htm. Accessed September 3, 2014.

2. Centers for Disease Control and Prevention. CDC estimates of 2009 H1N1 influenza cases, hospitalizations and deaths in the United States. www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm. Accessed February 1, 2014.

3. US Department of Health and Human Services. Pandemic flu history. www.flu.gov/pandemic/history/.Accessed September 3, 2014.

4. Dolin R. Influenza. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. Columbus, Ohio: McGraw-Hill Education; 2011. Accessed September 13, 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=331&Sectionid=40726944.

5. Centers for Disease Control and Prevention. Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed, 2nd printing. Washington, DC: Public Health Foundation; 2012.

6. Flu Activity & Surveillance. Centers for Disease Control and Prevention website. www.cdc.gov/flu/weekly/fluactivitysurv.htm. Accessed September 1, 2014.

7. Are you ready for flu? CDC’s recommendations and communication plans for the 2014-2015 influenza season [webinar]. www.vicnetwork.org/2014/08/14/are-you-ready-for-flu-cdcs-recommendations-and-communication-plans-for-the-2014-2015-influenza-season/. Accessed September 3, 2014.

8. Centers for Disease Control and Prevention. Estimated influenza illnesses and hospitalizations averted by influenza vaccination — United States, 2012-13 influenza season. MMWR Morb Mortal Wkly Rep. 2013:62(49);997-1000.

9. Tinoco JC, Pavia-Ruz N, Cruz-Valdez A, et al. Immunogenicity, reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults ≥18 years: a phase III, randomized trial. Vaccine. 2014;32(13):1480-1487.

10. Grohskopf LA, Olsen SJ, Sokolow LZ, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices — United States, 2014-15 influenza season. MMWR Morb Mortal Wkly Rep. 2014:63(32);691-697.

11. Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. Update on influenza vaccine safety monitoring. Presented at the Advisory Committee on Immunization Practices meeting, June 2013, Atlanta, Ga. www.cdc.gov/vaccines/acip/meetings/meetings-info.html.

12. Centers for Disease Control and Prevention. Live attenuated influenza vaccine [LAIV] (the nasal spray flu vaccine). www.cdc.gov/flu/about/qa/nasalspray.htm. Accessed September 13, 2014.

13. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;37:635-645.

14. Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older.

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15. Flucelvax [package insert]. Cambridge, MA: Novartis; March 2014.

16. Flublok [package insert]. Meriden, CT: Protein Sciences Corp; March 2014.

17. Des Roches A, Paradis L, Gagnon R, et al. Egg-allergic patients can be safely vaccinated against influenza.

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18. Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) — United States, 2011. MMWR Morb Mortal Wkly Rep. 2011:60(33);1128-1132.

19. Centers for Disease Control and Prevention. National early season flu vaccination coverage, United States, November 2013. www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2013.htm. Accessed September 3, 2014.

20. Fluzone [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

21. Fluzone High-Dose [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

22. Fluzone Intradermal [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

23. Fluzone Quadrivalent [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

24. FluLaval [package insert]. Quebec City, QC, Canada: ID Biomedical Corporation of Quebec; May 2014.

25. FluLaval Quadrivalent [package insert]. Quebec City, QC, Canada: ID Biomedical Corporation of Quebec; May 2014.

26. Afluria [package insert]. Parkville, Victoria, Australia: bioCSL; August 2014.

27. Fluvirin [package insert]. Speke, Liverpool, UK: Novartis; February 2014.

28. Flumist [package insert]. Gaithersburg, MD: MedImmune; July 2014.

29. Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline; 2014.

30. Fluarix Quadrivalent [package insert]. Dresden, Germany: GlaxoSmithKline; 2014

31. Centers for Disease Control and Prevention. Table: Influenza vaccines — United States, 2014-15 influenza season. www.cdc.gov/flu/protect/vaccine/vaccines.htm. Accessed on September 3, 2014.