Seasonal Influenza

Immunization Strategies for Older Adults

Planning Committee

Program Leads

• Shelly McNeil, MD, FRCPC

• Paul Van Buynder, MBBS, MPH, FAFPHM

Expert Reviewers

• John Axler, MD, FCFP, CCFP

• Phyllis Bedder, MD

• Sol Stern, MD, MSc, BSc, MCFP

• William Schaffner, MD

Learning Objectives

After successful completion of the program, the participant will be

able to:

• Describe burden of influenza in adults aged 65 and older.

• List the vaccine options available for seasonal influenza

immunization of adults aged 65 and older.

• Differentiate vaccine products approved for seasonal influenza in

adults aged 65 and older.

• Effectively counsel older adult patients about the importance of

seasonal influenza vaccination.

Vaccine abbreviations used in this program

• TIV = trivalent inactivated virus vaccine

• aTIV = MF59-adjuvanted TIV

• hdTIV = high-dose TIV

• QIV = quadrivalent influenza virus vaccine

Influenza Immunization for Adults 65+ Years

• burden of influenza-related illness

• age-related changes in immunity

• current opportunities for stimulating influenza immunity

• importance of immunization

Influenza Virus

• 3 types: A,B,C (A and B cause seasonal influenza epidemics)

• Influenza A subtypes: based hemagglutinin (H) and neuraminidase (N), e.g., H1N1 or H3N2

• Influenza B strains: B/Yamagata and B/Victoria

In Canada:1

• Influenza and pneumonia = a top 10 cause of death

• 23,000 cases/year

• 2,200 hospitalizations

• 3,500 deaths

• … but under-reported!

The World Health Organization (WHO) Naming

Convention

• The antigenic type (e.g., A, B, C)

• The host of origin (e.g., swine, equine, chicken, etc. For human-origin

viruses, no host of origin designation is given.)

• Geographical origin (e.g., Denver, Taiwan, etc.)

• Strain number (e.g., 15, 7, etc.)

• Year of isolation (e.g., 57, 2009, etc.)

• For influenza A viruses, the hemagglutinin and neuraminidase

antigen description in parentheses (e.g., (H1N1), (H5N1))

Seasonal Epidemics Caused by:

• Influenza A: including subtypes (H1 or

H3) + (N1 or N2)

• Influenza B: including lineages

B/Yamagata- and B/Victoria-like viruses

Strain Effects

Influenza A

• associated with the most significant burden of illness; vast majority of hospitalizations and deaths

• A(H3N2) - impact on the older adult population + comorbidity

• level of circulation linked to seasonal surges in all-cause mortality and hospitalizations

• Influenza-attributable pneumonia and influenza hospitalizations, as well as respiratory and circulatory hospitalizations, are greatest in influenza A (H3N2) predominant seasons

Influenza B

• usually affects younger population, but worse outcomes in older adults

Practice Tip

• Remind older adult patients that the flu virus changes from year to

year, so it is important to get your shot every year

Atypical Presentation in Older Adults

• Fever?

• Lower respiratory tract symptoms

• Atypical complaints e.g., anorexia,

mental status changes, and

unexplained fever

• Worsening respiratory status in COPD

and heart failure

• Pneumonia

• Gastrointestinal symptoms

Burden in Older Adults

In adults aged 65 and older in Canada:

• Influenza-related hospital admissions occur in 125 to 228 per

100,000 healthy individuals. 1

• Mortality rates increase with increased age.1

• Can trigger myocardial infarction or strokes9,10

Burden in Older Adults

Age-related decline in immune function impairs both the ability to resist

influenza infection and to respond to influenza vaccination6

• Majority of influenza-related deaths; also excess mortality from

cardiovascular diseases, strokes, diabetes, and pneumonia

• Loss of independence in the activities of daily living and diminished

quality of life

• Serious disability: influenza, pneumonia, and cardiovascular

complications

• Expected rise in permanent disability for aging population due to

influenza-related illness

The Unmet Need

• Goal of 80% unmet

• In the 2015-2016 season, coverage was only 65

• Influenza immunization decreases the incidence of pneumonia,

hospitalization, death

• Immunosenescence: standard influenza vaccines (TIV or QIV)

produce a weaker response in older adults; enhanced vaccines

designed to address this need

• High burden of A(H3N2) - need to improve immunogenic vaccine

effectiveness14

Unique needs of older patients, newer vaccine options

Madeline

• 72 years of age

• good overall health; mild hypertension

• recently re-married, likes to travel

• 5 grandchildren

• Currently October; will be travelling and

visiting grandchildren

• due for seasonal influenza

immunisation

Case Challenge

• “I am not old! I’m quite young and

strong still. And I never get sick.”

Case Challenge

“I am not old! I’m quite young and strong still. And I never get sick.”

What age group is identified as especially recommended for influenza

immunization due to age-related decline in immunity?

a) Adults age 50 and older

b) Adults age 65 and older

c) Adults age 70 and older

d) Adults age 75 and older

Counselling

• As people are living longer than ever before, some might disregard

the increasing importance of getting their ‘flu shot’ after age 65 simply

because they still feel young and strong.

• A recommended approach to providing vaccination is to make a

short, affirmative statement (e.g., “It is time for your flu shot.”)

Important Counselling Messages

• Get your flu shot. The shot is the best

way to prevent the flu.

• The flu can be serious.

• The shot is especially important for

people age 65 and older.

• There are 2 types of vaccines especially

made for people 65 and older. One is a

high-dose vaccine and the other is

called an adjuvanted vaccine.

Additional Protection

• Take care of your overall health.

• Practice preventive habits.

• See your doctor right away if you think

you might have the flu.

• Stay up to date on all recommended

shots.

Case Challenge

Which of the following types of vaccine

are options for Madeline?

a) TIV, standard dose

b) TIV, MF59-adjuvanted

c) TIV, high dose

d) QIV

e) LAIV

f) a, b, or c

g) a, b, c, or d

h) All of the above

LAIV = live attenuated influenza vaccine; TIV = trivalent influenza vaccine; QIV = quadrivalent influenza vaccine

Influenza Vaccines

• SOS Network: pooled effectiveness

data from 3 seasons was 41.7%, and

39.3% in adults aged 65 and older17

• Vaccines are reformulated annually to

account for drift

• TIV contains 3 virus (2A + 1B); QIV

contains 2A + 2B

See Table 3 of the Canadian Immunization Guide Chapter on

Influenza and Statement on Seasonal Influenza Vaccine for 2017–

2018 too view vaccines indicated in adults age 65 and older in

Canada for the 2017-2018 season

Vaccine Products

Product Type

(abbreviation)

Product Type Route of

Administration

TIV trivalent inactivated

vaccine

IM

QIV quadrivalent influenza

vaccine

IM

aTIV MF59-adjuvanted trivalent

vaccine

IM

hdTIV

trivalent inactivated

vaccine, quadruple dose

IM

IM = intramuscular injection

Immunosenescence

• Innate immunity declines with age.

• Immunosenescence makes vaccine immunogenicity a challenge in

older adults.

• Vaccination in this group is a high priority since influenza infection

carries the highest risk of serious outcomes in this group.

Cross-Protection

• Heterotypic antibody protection (cross-protection) occurs when

vaccine effectiveness against one strain confers a cross-strain

effectiveness against another strain

• Efficacy of influenza vaccines depends on the degree of similarity to

strains in circulation, as well as the age and immunocompetence of

the vaccine recipient

• Vaccines have variable ability to provide cross-protection

• High heterogeneity of circulating influenza viruses makes cross-

protection desirable

• Example = H3N2

Enhanced Vaccines

Enhanced influenza vaccines were developed to address challenges in

the aging population, specifically:

• immunosenescence

• the burden illness, particularly associated with A(H3N2

• to bridge the antigenic gap between circulating and vaccine strains

• Two vaccine formulation strategies have been introduced, which aim

to improve immunogenicity over standard TIV:

adjuvanted TIV (aTIV)

high-dose TIV (hdTIV)

Adjuvanted Trivalent Influenza Vaccine

The MF59 adjuvant contained in aTIV is an oil-in-water emulsion

composed of squalene as the oil phase, stabilized with the surfactants

polysorbate 80 and sorbitan trioleate, in citrate buffer

O’Hagan DT, et al. Vaccine. 2012;30(29):4341–8.

aTIV Mechanism of Action

More antibodies target the ‘head’ of the hemagglutinin antigen

aTIV Safety and Efficacy

• higher immunogenicity of aTIV over TIV across strains, particularly

against A/H3N2

• longer duration of enhanced immune response over the influenza

season

• greater breadth of the immune response, with aTIV showing higher

immunogenicity against heterotypic strains

• local reactions at injection site

aTIV Successes in Older Adults

Adjuvanting increases vaccine immunogenicity, resulting in

comparatively higher levels of haemagglutination inhibition antibodies,

and greater protection against all influenza.

• Canadian study: efficacy of 63% in adults 75+ years; no efficacy was

seen with standard TIV.52

• Northern Italy, the LIVE Study: increased efficacy of aTIV of 25%

versus standard TIV against pneumonia-related or influenza-related

hospitalisation, despite use in frail elderly.53

• Systematic review and meta-analysis suggested that aTIV, compared

with a conventional non-adjuvanted TIV, is effective in reducing

influenza-related outcomes in older adults, particularly

hospitalisations.54

High Dose TIV

• 4X dose

• 60 µg of haemagglutinin (HA) per strain, compared to 15 µg HA per

strain in a standard dose, administered as a single 0.5 mL dose by

intramuscular injection

• The hdTIV for older adults was designed to provide superior

protection26

TIV 15 µg HA per strain X4

hdTIV Efficacy and Safety

• Phase III trials: higher antibody response and reduced laboratory-

confirmed influenza versus standard TIV55,56

• Enhanced protection against serious, life-threatening pneumonia

associated with influenza.57

• The safety profile of high-dose TIV is similar to that of standard TIV55

hdTIV Success in Older Adults

• Phase 2 and 3 studies: antibody response was significantly higher

than that induced by standard TIV vaccine

• Retrospective cohort study of over 2 million people in the US:

significantly more effective than standard-dose vaccine in prevention

of influenza-related hospital admissions

• 22% more effective than the standard TIV

• 22% more effective for prevention of influenza hospital admissions

• Real world studies: significantly more effective than standard TIV in

the prevention of influenza-related medical encounters,

hospitalizations, and death

Case Challenge 3

Which of the following types of vaccine

are expected to provide greatest

immunogenicity for Madeline?

a) TIV or QIV, standard dose

b) TIV, high dose

c) TIV, MF59-adjuvanted

d) b or c

Population-Based Protection

• Vaccination of healthcare practitioners has a protective effect on

residents of long-term care facilities, including reduced mortality

among patients

• Influenza vaccination of healthcare personnel is currently

recommended in over 40 countries

• Vaccination of all individuals over 6 months of age helps to establish

community protection (herd-immunity) against influenza. Since

children play an important role in the transmission of influenza, they

are an important group for vaccination, even beyond their own

protection.

• Vaccination of all older adults also contributes to herd immunity

Conclusion

• Annual influenza immunization of people age 65 and older is the best

protection available against influenza. Influenza vaccines are among

the safest vaccines in the world, and influenza immunization is cost-

effective in this group

• Annual influenza vaccination of the older adult population is the

primary strategy for disease prevention and control.27

• Enhanced vaccines provide superior protection versus standard TIV

in this group and should be selected wherever possible

• Additional measures to limit transmission include vaccinating those in

proximity to the patient, including children, as well as preventive

behaviours such as hand-washing

Key Points

• Older adults have higher burden of influenza-related illness,

hospitalization, and death from influenza due to immunosenescence

and suboptimal response to standard influenza vaccines, especially

to A(H3N2).

• Influenza vaccination reduces complications and long-term risks.

• Immunosenescence in people age 65 and older contributes to loss of

both existing influenza immunity and impaired immune response to

vaccination.

• Enhanced vaccines (aTIV, hdTIV) confer greater benefits for

overcoming the problem of immunosenescence after age 65 than

standard TIV.

Key Points

• The MF59 adjuvant in aTIV was designed to both enhance and

broaden the immune response to influenza compared to standard

TIV. The use of aTIV can confer improved immunity, including

heterotypic immunity for those age 65 and older.

• The hdTIV vaccine provides quadruple the dose of standard TIV, for

an enhanced vaccine response compared to standard-dose TIV.

• When vaccinating older adults, identify people who are high-priority

for influenza vaccination including family members and others who

are near to them.

Resources

Canadian Immunization Guide Chapter on Influenza and Statement on

Seasonal Influenza Vaccine for 2017–2018

Public Health Agency of Canada (PHAC) - Immunization and Vaccines

National Advisory Committee on Immunization (NACI)

Immunize Canada

Frequently asked Questions (video with Dr Paul Van Buynder)

FluWatch (Flu surveillance)

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