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Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations
Miranda Wilhelm, PharmD
Participating Faculty
Posttest

Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations

Miranda Wilhelm, PharmD
Older patients typically do not mount as strong an immune response to vaccines as do younger patients. Even with vaccination, older people are less likely to achieve full protection. In a quantitative review of 31 studies that compared antibody responses to influenza vaccines in adults, younger adult populations achieved 70% to 90% seroconversion and seroprotection rates, and older populations achieved considerably reduced rates of approximately 17% to 53%.25 The reason for this is unknown, but immunosenescence and blunting of immune response due to repeated prior immunization have been put forth as hypotheses.26 Regardless of the reason, there remains a need for improved vaccine seroconversion and seroprotection among older patients.

This section will focus on the delivery of influenza vaccine to adults 65 years or older. The package inserts of vaccine formulations may contain additional information relevant to the administration of the product to children and other special populations. The reader is encouraged to consult this information for people younger than 65 years, as significant differences may exist between populations.

2017-2018 Advisory Committee on Immunization Practices Influenza Vaccine Recommendations

The CDC recommends use of injectable vaccines, either inactivated virus or recombinant influenza vaccines.1 The nasal spray influenza vaccine is not recommended for any groups of people during the 2017-2018 influenza season, according to the Advisory Committee on Immunization Practices (ACIP).27 The nasal spray vaccine is indicated for patients 2 to 49 years of age in other years. Influenza vaccines are composed of either 3 or 4 components that are intended to provide immunity to 2 A type and 1 or 2 B type influenza viruses. Of influenza A type viruses that were sequenced in the 2016-2017 season (77.9% of all influenza viruses), 97.2% were influenza A (H3N2) viruses and 2.8% were influenza A (H1N1)pdm09 viruses (the virus that caused the 2009 pandemic). Of influenza B type viruses that were sequenced, 71.2% belonged to the B/Yamagata lineage and 28.8% to the B/Victoria lineage.16

For the 2017-2018 season, influenza vaccines have been updated to better match circulating viruses.16 The FDA Vaccines and Related Biologic Products Advisory Committee has recommended that the 2017-2018 influenza trivalent vaccine to be used in the United States contain an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like (B/Victoria lineage) virus. The quadrivalent vaccine is to contain the viruses in the trivalent vaccine, plus a B/Phuket/3073/2013-like (B/Yamagata lineage) virus. The major difference this year from last is the updating of the A (H1N1) viral component.

Available Vaccine Products

The Table lists the various types of available vaccine products. Inactivated influenza vaccines (IIV) have 15 mcg of each HA antigen (45 mcg total in trivalent, and 60 mcg total in quadrivalent vaccines).27 Adults 65 years or older may receive any age-appropriate influenza vaccine (Table). This may include standard- or high-dose, trivalent (IIV3) or quadrivalent (IIV4), and adjuvanted (aIIV) or unadjuvanted vaccine. Sometimes, standard-dose IIV3 is referred to as “IIV3-SD,” when there is a need to distinguish it from the high-dose (IIV3-HD) vaccine. Single-dose vials do not contain thimerosal, although multidose vials most often do. All influenza vaccines intended for adults 65 years or older are delivered via intramuscular injection.

Trivalent Influenza Vaccines

Influenza vaccines were developed for use by the US military and, in the early 1960s, the use was expanded to high-risk populations, including adults 65 years or older.28 Traditionally, these vaccines have 3 components (ie, trivalent): 2 A-type viral products and 1 B-type. To date, data from adequately powered trials have shown vaccine effectiveness of 40% to 60% in adults 50 years or older when circulating and influenza vaccine strains are similar.26 However, adequately powered trial data are lacking for the cohort of adults 65 years or older.

Trivalent, Standard-Dose, Inactivated Influenza Vaccines

A standard-dose, trivalent, inactivated influenza vaccine (Afluria [IIV3]) is available for people 5 years or older.29 It is purified from the allantoic fluid of embryonic chicken eggs over a sucrose density gradient, inactivated with β-propiolactone, and disrupted with mild detergent (sodium taurodeoxycholate) to produce a “split-virion.” The vaccine contains greater than trace amounts of detergents, ovalbumin, antibiotics (neomycin sulfate, polymyxin B), and β-propiolactone.

Another standard-dose, trivalent, inactivated influenza vaccine (Fluvirin [IIV3]) available is for people 4 years or older.30 The antigens are purified from influenza virus produced in eggs. Hemagglutinin and neuraminidase antigens are purified by zonal gradient centrifugation. Trace amounts of egg and viral proteins, antibiotics (neomycin sulfate, polymyxin B), detergents, polymers used during purification, and thimerosal may remain.

Trivalent, Standard-Dose, Recombinant Influenza Vaccines

The recombinant, trivalent, standard-dose influenza vaccine (Flublok [RIV3]) is an egg-free, recombinant hemagglutinin product, produced in cell culture (insect cells) grown in serum-free media, that is available for individuals 18 years and older.31 Hemagglutinin protein from each of the 3 influenza strains is purified and mixed to provide 45 mcg of each (135 mcg total). This product is of significant benefit to those persons with severe egg allergy, defined as symptoms greater than hives alone after influenza vaccination (eg, bronchospasm). It is free of infectious influenza virus, antibiotics, thimerosal, preservatives, gelatin, and latex.

High-Dose, Adjuvanted, and Quadrivalent Influenza Vaccines

To circumvent deficient immunity in older people, vaccine manufacturers have created high-dose and adjuvanted vaccines, with the goal of provoking a stronger immune response.

Trivalent, High-Dose, Inactivated Influenza Vaccines

A trivalent, inactivated, split-virion, high-dose influenza vaccine (Fluzone High-Dose [IIV3-HD]) is indicated for use in adults 65 years or older.32 It is produced in eggs and purified through sucrose density gradient centrifugation. High-dose formulations contain 60 mcg hemagglutinin of each influenza strain, as compared with 15 mcg hemagglutinin of each strain in standard-dose influenza vaccines. IIV3-HD vaccines induce substantially greater antibody responses and better protection against influenza and influenza-associated hospitalization than IIV3-SD.33 In a study of 31,989 participants, 1.4% of those receiving the high-dose formulation had laboratory-confirmed influenza, compared with 1.9% of those receiving the standard dose.32 Persons receiving the high-dose formulation also experienced higher hemagglutination-inhibition (HAI) titers and reduced incidence of serious adverse effects.32 It has been suggested that, due to improved coverage and prevention of illness, IIV3-HD may provide cost savings compared with IIV3-standard dose in older patients.34,35

Trivalent, Standard-Dose, Inactivated, Adjuvanted Influenza Vaccines

A trivalent, standard-dose, inactivated, adjuvanted influenza vaccine (Fluad [aIIV3]) is available for use in patients 65 years or older.36 It is produced by the same methods as Afluria. In addition, the adjuvant MF59C.1 is included. MF59C.1 is a squalene-based, microfluidized (oil in water) emulsion.37 It activates monocyte transition to dendritic cells, recruitment of antigen-presenting cells, and antigen uptake. A pooled analysis of case-controlled studies found an adjusted vaccine effectiveness of 51% for adjuvanted trivalent influenza vaccination, with an effectiveness against laboratory-confirmed influenza of 61.1%.37 The MF59C.1 adjuvanted trivalent vaccine reduced hospitalizations (aRH, 0.75) and laboratory-confirmed influenza (aOR, 0.37), as compared with nonadjuvanted vaccine.

Quadrivalent, Standard-Dose, Inactivated Influenza Vaccines

A quadrivalent, standard-dose, inactivated influenza vaccine (Afluria Quadrivalent [IIV4]) is available, manufactured by the same methods as Afluria trivalent.38 It is approved for patients older than 5 years.

A second split-virion, quadrivalent, inactivated influenza vaccine (Fluzone Quadrivalent [IIV4]) is approved for use in patients 6 months or older.39 It is produced in eggs, purified in a sucrose gradient, inactivated with formaldehyde, and disrupted with detergents. Greater than trace amounts of ovalbumin, formaldehyde, and detergents may remain. Unlike most influenza vaccines, antibiotics are not used during the manufacture of this vaccine.

There is a split-virion, quadrivalent, inactivated influenza vaccine (Fluarix Quadrivalent [IIV4]) that is approved for use in patients 3 years or older.40 It is produced in eggs, purified by zonal sucrose gradient, and disrupted with sodium deoxycholate and formaldehyde. Greater than trace amounts of residual detergents, hydrocortisone, ovalbumin, and formaldehyde may remain.

Another split-virion, inactivated, quadrivalent influenza vaccine (FluLaval Quadrivalent [IIV4]) is available for use in patients 6 months or older.41 It is produced in eggs and inactivated by formaldehyde and ultraviolet light and disruption with sodium deoxycholate. Greater than trace amounts of ovalbumin, formaldehyde, and detergents may remain. It is also free of antibiotics.

Quadrivalent, Standard-Dose, Recombinant, Inactivated Influenza Vaccines

There is a recombinant, quadrivalent, standard-dose, inactivated influenza vaccine (Flublok Quadrivalent [RIV4]) that is an egg-free, recombinant hemagglutinin product produced in cell culture.42 People with egg allergies may receive this or the trivalent influenza vaccine (Flublok). It is free of infectious influenza virus, antibiotics, thimerosal, preservatives, gelatin, and latex. Results of a single study involving 8963 adults (mean age, 62.5 years) during the 2014-2015 influenza season showed that the recombinant vaccine (RIV4) was more efficacious than the quadrivalent, inactivated virus vaccine (IIV4), and that people receiving it were 30% less likely to become ill with laboratory-confirmed influenza.42,43 However, the FDA did not allow the manufacturer to claim superiority of this RIV4 over other IIV4 vaccines.44

Quadrivalent, Standard-Dose, Inactivated Influenza Vaccines Produced in Cell Culture

A recombinant, quadrivalent, standard-dose inactivated influenza vaccine (Flucelvax Quadrivalent [RIV4]) that is produced in cell culture is an egg-free, recombinant hemagglutinin product produced in immortalized Madin-Darby Canine Kidney cells.45 It is approved for use in people 4 years or older. It does not contain ovalbumin, antibiotics, or natural latex.

Quadrivalent, Standard-Dose, Intradermal, Inactivated Influenza Vaccines

 
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