1. Influenza Vaccines Immunization Update: Maine Pharmacy Association
April 1, 2017
Brooke Cowles, PharmD
PGY-1 Pharmacy Resident & Clinical Instructor | UNE

5. ACIP Recommendations 2016-17 Influenza Season
For 2016–17, U.S.-licensed trivalent influenza vaccines contain:
A/California/7/2009 (H1N1)-like virus
A/Hong Kong/4801/2014 (H3N2)- like virus
B/Brisbane/60/2008-like (B/Victoria lineage) virus.
This represents changes in the influenza A (H3N2) virus and the influenza B virus as compared with the 2015–16 season. Quadrivalent influenza vaccines will contain these vaccine viruses, and a B/Phuket/3073/2013-like (B/Yamagata lineage) virus.
All persons aged ≥6 months should receive influenza vaccine annually.
In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013–14 and 2015–16 seasons, for the 2016–17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used.
The current influenza vaccine has been 48% (95% confidence interval [CI], 37% - 57%) effective in preventing influenza-related medical visits in all age groups, the CDC reported on February 17. According to the report, the vaccine was 43% (95% CI, 29% - 54%) effective against influenza A (H3N2) viruses and 73% (95% CI, 54% - 84%) effective against influenza B–related illness.

9. ACIP Recommendations 2016-17 Influenza Season
Persons with a History of Egg Allergy
Those who only have hives after exposure to egg can receive any age- appropriate inactivated influenza virus (IIV) or recombinant influenza virus (RIV3)
Those who report having other reactions besides hives (e.g. angioedema, respiratory distress, lightheadedness, or recurrent emesis) may receive any age-appropriate IIV or RIV3 vaccine as long as it is administered in an inpatient or outpatient medical setting
Those who have had a previous severe allergic reaction to an influenza vaccine are contraindicated
*Consider observing all patients for 15 minutes postvaccination*

10. Vaccinating Those with a History of Egg Allergy
A VSD study with over 25.1 million doses of vaccine of various types (not just influenza vaccine) administered to children and adults revealed a total of 33 cases of reactions consistent to anaphylaxis
In 8 cases, symptoms began within 30 minutes of vaccination
In 21 cases, symptom onset was > 30 minutes postvaccination
When 7.4 million doses of IIV3 were given, there were 10 cases of anaphylaxis
1.35 per 1 million doses of IIV31
Reviews of studies of experience with use of IIV and LAIV indicate that severe allergic reaction with egg allergy are unlikely
In 2012, out of 4,172 egg-allergic patients (513 of those reporting history of severe allergic reaction) there were no noted occurrences of anaphylaxis, though there were milder reactions2
Mild reactions included 1 person with uticara, 2 vomiting, and 1 with eczema
1. McNeil MM et al. J Allergy Clin Immunol. 2016; 137:
2. Des Roches A et al. J Allergy Clin Immunol. 2012; 130:

11. Select the TRUE statement:
ACIP does not recommend LAIV for the influenza season
ACIP continues to recommend annual influenza vaccine for 6 mos and older
LAIV is not recommended due to concerns regarding low effectiveness
All statements are true

12. Adults with a history of egg allergy who have symptoms other than hives (e.g., angioedema, respiratory distress, lightheadedness, or recurrent emesis) may receive age appropriate inactivated influenza vaccine or recombinant influenza vaccine when administered in an inpatient or outpatient medical setting.
True
False

13. Influenza Vaccine
The Vaccines and Related Biological Products Advisory Committee of the FDA selected the strains of influenza vaccine for the season
For the trivalent vaccine it will contain:
A/Michigan/45/2015 (H1N1)pdm09-like virus
A/Hong Kong/4801/2014 (H3N2)-like virus
B/Brisbane/60/2008-like virus (B/Victoria lineage)
For the quadrivalent vaccine it will also contain:
B/Phuket/3073/2013-like virus (B/Yamagata)
The only change is the H1N1 strain, however, this was the same strain recommended for the southern hemisphere in 2017
FDA Committee Selects Influenza Vaccine Strains. Medscape. Mar 10, 2017.

14. Recently Licensed Influenza Vaccine Products

15. Adjuvanted Trivalent Inactivated Influenza Vaccine Fluad®

16. Adjuvanted Trivalent Vaccine
FDA approved November 2015 for people ages 65 and older
Adjuvanted, inactivated, trivalent vaccine (Seqirus)
Fluad also contains MF59C.1 (MF59®), a squalene based oil-in-water emulsion
First adjuvanted influenza vaccine in the United States
To date, there have been no randomized studies to compare Fluad with Fluzone High Dose

17. S.E. Frey et al. Vaccine. 32 (2014) 5027–5034.
In , subjects (N=7082) were randomized to receive one dose of aTIV or TIV
Primary Objectives:
Assess lot-to-lot consistency of aTIV, non-inferiority, superiority, and immunogenicity 22 days after vaccination
Results:
Immunological equivalence was established and aTIV was found to be non-inferior to TIV
S.E. Frey et al. Vaccine. 32 (2014) 5027–5034.

18. S.E. Frey et al. Vaccine. 32 (2014) 5027–5034.
Fig. 2. Geometric mean ratio (GMR), percentage of subjects showing seroconversion and percentage of subjects seroprotected (±95% CI) for all (A) homologous and (B)heterologous strains at Day 22 post-vaccination. Lines represent the relevant CHMP criterion for each measure. Data presented are for the full analysis set.
S.E. Frey et al. Vaccine. 32 (2014) 5027–5034.

19. % of adults >65 years with local adverse reactions in days 1-7
S.E. Frey et al. Vaccine. 32 (2014) 5027–5034.

20. % of adults >65 years with systemic adverse reactions in days 1-7
S.E. Frey et al. Vaccine. 32 (2014) 5027–5034.

21. Administration Dose: 0.5 mL
Inject: IM into deltoid with 1 inch, 25 gauge needle
Storage: Store Fluad® at 2°C - 8°C ( °F)
Gently shake each syringe
Fluad Package Insert

22. Vaccine Products: 2016 – 2017 Season

23. Inactivated, Trivalent Recombinant Vaccine Flublok® (Protein Sciences)

24. Trivalent Recombinant Vaccine
FDA approved November, 2013 for adults 18 years and older
Trivalent inactivated vaccine grown in insect cells rather than chicken embryo cells
Doesn’t list “severe allergic reaction to egg protein” in the contraindications
Does not contain egg proteins, antibiotics, or preservatives

25. Frequency of Local and Systemic Reactions within 7 days of Flublok or Placebo in Adults 18-49 years

26. Administration Dose: 0.5 mL
Inject: IM into the deltoid with 1 inch, 25 gauge needle
Storage: Store Flublok® at 2°C - 8°C ( °F)
Gently shake before administering

27. High-Dose Inactivated Influenza Trivalent Vaccine (IIV) Fluzone HD® (Sanofi Pasteur)

28. High Dose Trivalent Vaccine
FDA approved in 2009 for adults 65 years of age and older
Contains more hemagglutinin per vaccine virus strain compared to a standard inactivated influenza vaccine
60 µg per strain vs. 15 µg per strain
At this point, there is no preferential recommendation between aIIV3, standard-dose IIV, or high-dose IIV3 for those aged ≥ 65 years

29. Methods: Retrospective cohort study
HD vaccine (60 mcg of hemagglutinin per strain): N= 929,730
SD vaccine (15 mcg of hemagglutinin per strain): : N= 1,615,545
US Medicare beneficiaries 65 years and older who received influenza vaccine in a community pharmacy
Primary outcome: probable episode of influenza-related illness defined by a community medical encounter with the provision of a rapid influenza test followed by dispensing of oseltamivir within a 2-day period
Lancet Infect Dis 2015;15:
Lancet Infect Dis 2015;15:

30. Efficacy of HD Vaccine versus SD Vaccine Against Influenza-Related Illness
Similar results to Diazgranados et al.
Those who received IIV-HD 22% less likely to have influenza-associated illness and 22% less likely to be admitted to the hospital for influenza
Each plot displays the rate of influenza per person-weeks. Data was smoothed using a weighted average,
placing a weight of 0・5 on the current week and a weight of 0・25 on the previous and following weeks. (A) Rapid
infl uenza test followed by treatment with oseltamivir. (B) Inpatient hospital admissions or emergency department
visits with an infl uenza International Classifi cation of Diseases, ninth revision, Clinical Modifi cation code. RIT=rapid
infl uenza diagnostic test.
Lancet Infect Dis 2015;15:

31. Administration Dose: 0.5 mL
Inject: IM into the deltoid with 1 inch, 25 gauge needle
Storage: Store Fluzone HD® at 2°C - 8°C ( °F)
Gently shake before administering

32. Inactivated Influenza Vaccine (IIV) Quadrivalent Fluarix®, FluLaval®, Fluzone®, Fluzone Intradermal®

33. IIV Quadrivalent Fluarix® (GlaxoSmithKline)
FDA approved December 2012
People ages 3 years and older
Fluzone Quadrivalent® (Sanofi Pasteur)
FDA approved March 2013
People ages 6 months and older
Flulaval® (GlaxoSmithKline)
FDA approved in 2013

34. Administration Dose: 0.5 mL
Inject: IM into the deltoid with 1 inch, 25 gauge needle
Storage: Store at 2°C - 8°C ( °F)
Flulaval multi-dose vial must be discarded 28 days
once entered
Gently shake before administering
Afluria also has the same discard date once entered

35. Intradermal Influenza Vaccine
FDA approved in 2014 for persons 18 through 64 years of age
Associated with higher rates of injection site reactions (erythema, induration, swelling, and pruritus, but not pain) than the IM inactivated influenza vaccines
Erythema (>75%)
Induration (>50%)
Swelling (>50%)
Pain (>50%)
Pruritus (>40%)

36. Comparison of local side effects to ID and IM influenza vaccine
Percent
Human Vaccines. 2010;6:

37. Intradermal Injection Technique
Remove needle cap
Hold microinjection system between thumb and middle finger
Do not place fingers on the windows
Insert needle rapidly perpendicular to the skin
Inject using the index finger
Remove needle from the skin and activate the needle shield by pushing firmly on the plunger
Fluzone Intradermal Package Insert

38. Which side effect is more common with the intradermal influenza vaccine than the IM influenza vaccine?
Headache
Fever
Injection site swelling
Malaise

39. Live Attenuated Influenza Vaccine (LAIV) Quadrivalent Flumist® (MedImmune)

40. Live Attenuated Influenza Vaccine
FDA approved in March 2012 for healthy people ages 2 through 49 years
Is not recommended in children 6 – 23 months of age due to increased risk of hospitalization and wheezing
Live attenuated vaccine which contains two type A and two type B strains
Flumist Package Insert

41. Live Attenuated Influenza Vaccine
Contraindications
Precautions
History of severe allergy to any component of the vaccine (including eggs)
Concomitant aspirin or salicylate-containing therapy in children & adolscents
Children aged 2-4 years who received a diagnosis of asthma or has had wheezing episode in past 12 months
Children & adults who are immunosuppressed
Close contacts & caregivers of severely immunocompromised persons
Pregnancy
Received antiviral medication within past 48 hours
Moderate to severe illness with or without fever
History of Guillain-Barre syndrome within 6 weeks of receipt of influenza vaccine
Asthma in persons aged ≥ 5 years
Other underlying medical conditions that might predispose to complications after wild-type influenza infection (COPD, CVD, renal, hepatic, or metabolic disorders)

42. Administration Dose: 0.1 mL into each nostril
Administed: Intranasally while patient is in the upright position
Storage: Store at 2°C - 8°C ( °F)
Keep in carton to protect from light

43. Influenza Vaccine Summary

44. Age Indication for Influenza Vaccines: United States, 2016-2017
0.5-2 years 2
years 3
4-8
9-17
18-49 years
50-64 years
65+
Fluzone / Fluzone Quad ✓
Flumist Quad
Fluarix Quad
FluLaval Quad
Fluvirin
Afluria1 +-
Flucelvax Quad
Flublok2
Fluzone Intradermal Quad
Fluzone High-Dose
Fluad Adjuvated Trivalent
“A licensed, age-appropriate vaccine should be used.”
Age indication via needle/syringe is >5 years and by Pharmjet needle-free injection is years.
FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+).

45. Characteristics of Influenza Vaccines: United States, 2016-17
Live
Mercury
Egg Protein
Latex
Fluzone / Fluzone Quad ✓1 ✓
Flumist Quad
Fluarix Quad
FluLaval Quad
Fluvirin ✓3
Afluria
Flucelvax Quad ✓2
Flublok
Fluzone Intradermal Quad
Fluzone High-Dose
Fluad Adjuvanted Trivalent
Multi-dose vials contain mercury. Single-dose prefilled syringes are mercury-free.
Estimated to contain <50 femtograms (5x10-8 mcg) of total egg protein per 0.5 ml dose.
Syringe tip may contain natural rubber latex.

46. Route of Admin. for Influenza Vaccines: United States, 2016-17
Young Children*
Older Children
Adults
Fluzone / Fluzone Quad
IM Thigh
IM Deltoid
Flumist Quad
Intranasal
Fluarix Quad
FluLaval Quad
Fluvirin
Afluria
Flucelvax Quad
Flublok
Fluzone Intradermal Quad
ID Deltoid
Fluzone High-Dose
Fluad Adjuvanted Trivalent
*Generally, less than 7 years old.

47. Select an influenza vaccine for a health 37-year old woman with severe egg allergy:
Flublok
Fluad
Fluzone
Fluarix

48. Select the multi-dose vial influenza vaccine that must be discarded 28 days after the stopper has been pierced:
Fluarix
Afluria
Flucelvax
Fluzone

49. Tips for an Ouch-Free Flu Shot
Do not prepare the vaccine in front of the patient.
Use a prefilled syringe or change the needle.
Make sure the alcohol is dry before injecting.
Ensure the patient’s arm is relaxed.
Inject into the deltoid at least 3 finger widths below the crest of the shoulder.
Distract kids; ask them to pretend they are blowing out candles on a birthday cake or blow on a pinwheel.

50. Questions & Discussion

51. References
1. Robinson CL, Romero JR, Kempe A et al. “Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older – United States, MMWR Feb; 66(5):
2. Grohskopf LA, Sokolow LZ, Broder KR, et al. “Prevention and Control of Seasonal Influenza with Vaccines Recommendations of the Advisory Committee on Immunization Practices – United States, Influenza Season. MMWR Aug; 65(5):1-36.
3. Des Roches, A, Paradis L, Gagnon R, et al. “Egg-allergic patients can be safely vaccinated against influenza.” J Allergy Clin Immunol. 2012; 130:
4. McNeil MM, Weintraub ES, Duffy J, et al. “Risk of anaphylaxis after vaccination in children and adults.” J Allergy Clin Immunol. 2016; 137:
5. Frey SE, Aplasca-De Los Reyes MR, Reynales H et al. “Comparison of the safety and immunogenicity of an MF59®-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine. 32 (2014) 5027–5034.