Transcript Vaccines

Preventing Infections
Adult Vaccines: Update 2016
Thomas M File, Jr MD MSc MACP FIDSA FCCP
Chair, Infectious Disease Division
Summa Health System, Akron, Ohio;
Professor of Internal Medicine,
Chair ID Section
Northeast Ohio Medical University
Rootstown, Ohio
Disclosures
• Recent research funding– Cempra, Pfizer,
• Consultant/Scientific Advisory Board—Actavis, Melinta, The Medicines Co.,
Merck, MotifBio, Nabriva, Tetraphase, Venatorx
• IDSA/ATS Guideline panels: CAP (1998-2007); HAP/VAP (present); Sinusitis;
Influenza
• UpToDate: author-CAP; HAP/VAP; Acute Bronchitis
Objectives
 Review new developments in adult vaccines
 Focus on Influenza, pneumococcal and Zoster
vaccines
 Additional comments: Meningococcal B; HPV
Adult Vaccination: which
vaccines for these 2 patients?
1.
40-year-old woman who has a history of asthma, otherwise healthy. She has come to
your office for a health screen for a school cafeteria job
2.
65-year-old male has come to your office for a physical examination. He has no medical
records, and reports that he has smoked for many years. Initial evaluation reveals mild
emphysema and diabetes.
• Which Vaccines: Influenza, pneumococcal
• zoster
Threats to Vaccines
•Falling rates
oOutbreaks:
pertussis
measles, mumps,
•Success of past vaccines
oLack
of awareness of disease that is
prevented
•Effects of anti-vacccine movement
oFear,
mistrust, ignorance
2013 Adult Immunization
Coverage, US
**Influenza Estimates 2013-14.
MMWR. Feb 6, 2015. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6404a6.htm#Tab2
Healthy People 2020 Objectives on Immunization and Infectious Disease. www.Healthypeople.gov/2020/.
Burden of Vaccine-Adult Preventable
Disease in the US
Disease
Annual Burden of Disease, United States
Influenza
200,000 hospitalizations; 36,000 deaths (> 90% in older
adults)
Invasive
pneumococcal
disease
44,000 cases, 4500 deaths (higher rates of both in older
adults and persons with comorbidities)
Hepatitis B
51,000 infections (95% adults); 2000-3000 deaths;
1.25 million with chronic HBV infection
Human
papillomavirus
6.2 million new infections (>4000 women die in US
annually; ? Male deaths)
Pertussis
10,454 cases reported in 2007 (3152 adults)
Severe illness in infants; often transmitted by older child or
adult
Zoster
1 million cases; risk for shingles and postherpetic neuralgia
increases with age
Physician-Patient Miscommunication
National Foundation for Infecgious Diseases. Surveys of consumers and physicians
2010
The Communications Breakdown:
need to give clear unambiguous message
Recommendation
“You
need to
get this
vaccine.”
OR
“I want
you to
get this
vaccine.”
VaccineMotivated
Patient
Not a Recommendation
“Do you
want this
vaccine?”
OR
“Think
about
getting the
vaccine.”
VaccineAmbivalent
Patient
Vaccines: Very high benefit/risk ratio
•All vaccines have possible side effects, most mild,
rarely severe
 The risk of disease far outweighs the risk of
vaccine
11
12
Influenza Vaccine
Efficacy of 15/16 vaccine: Estimated 60% per CDC
16
Influenza Vaccine
Neuraminidase
•Develop antibodies to
Hemagglutinin and
Neuraminidase
•For A and B
oTrivalent (2A; 1B)
oQuadrivalent (2A; 2B)
•Need annually
Changes (mutations)
o Waning immunity
o
Hemagglutinin
2015-2016/17 U.S. Influenza
Vaccine Composition
oA/California/7/2009
(H1N1)
• Unchanged
oA/Switzerland/9715293/2013
(H3N2)
•Change (for 16/17: A/Hong Kong/2014)
oB/Brisbane/60/2008-like
virus;Victoria
strain)
oB/Phuket/3073/2013-like virus
(Quadrivalent).
•Similar to last year (Yamagata Strain)
18
INFLUENZA VACCINE-Importance
oInfluenza
may lead to many complications in
adults
• secondary pneumonia
• exacerbation of underlying disease(i.e., chronic lung or heart
disease)
oInfluenza
virus changes antigens over time;
patients may therefore, not be immune because
of prior exposure
oEfficacy
• Depends on: 1. Immunogenicity; 2. Serotype match
• Recently varied 20-60% pending patient type
oCan
be given at SAME time as pneumococcal
vaccine
US Influenza Vaccines
Prepared from embryonated chicken eggs inoculated with specific strains of virus
• IIV3&4: ‘Killed’, injectable “All comers” 6 months and
older--Both Trivalent (TIV) and Quadrivalent)
• IIV4 Intradermal (Quad)

Approved May 2011 for 18-64 years [smaller needle]
• LAIV4: Live-attenuated, cold-adapted nasal (CANNOT replicate at body temperature)nasal spray



very minimal viral shedding; OK to give to nurses unless taking care
of severely immunocompromised patients
Indicated only for healthy people 2-50 years; All Quadrivalent
ACIP JUNE 2016-Recommends AGAINST due to low
efficacy
IIV, Inactivated Influenza vaccine; TIV, trivalent inactivated vaccine
*Falsey AR et.al. J Infect Dis. 2009;200:172-180.
INFLUENZA VACCINE (>65)
• IIV3-Fluzone High-Dose
o Contains
60 mcg each of the 3 Influenza antigens (compared to 15
each for regular TIV)
o
Slightly higher rate of MILD reactions
o Indications:
Patients > 65 years.
o Costs (est $32 vs $12)
o In large clinical trial was 24.2% more effective in preventing influenza
in adults > 65. (cost effective) NEJM 2014;371:635-45
• AIIV3-FLU AD
o Adjuvant
vaccine; MF59, an oil-in-water emulsion of
squalene oil
o higher immunogenicity
o ACIP : Non preferential
Cell culture Influenza Vaccines
• Flucelvax 
o In
place of chicken eggs, uses animal cells (Canine Kidney) as
host(reference strain obtained form virus originally grown in eggs);
Quadravalent
o Approved ≥ age 4
• Flublok 
o Recombinant
vaccine (RIV) — egg-free hemagglutinin influenza
vaccine produced by recombinant DNA technology using a
baculovirus (a virus that infects insects) that produces virus-like
particles, hemaglutinin (vaccine of choice for true egg allergy)
o Approved ages >18; Only 16 week shelf life; Trivalent
• Adverse events similar to other inactive vaccines
INFLUENZA VACCINE
Reduction in Hospitalizations for Cardiac disease and Strokes (Nichols et a. NEJM 348, April 3, 2003)
• Observational studies of large cohorts (140,000;
146,000), ’98-’99 AND ’99-’00, 3 HMOs,  age 65
• Vaccination against influenza associated with reduction in
hospitalization for :
o
o
o
o
Cardiac disease (19% both seasons)
Cerebrovascular disease (16%; 23%)
Pneumonia and Influenza (32%; 29%)
All cause Death (48%; 50%)
• Possible mechanisms: infection cause alterations in clotting
factors, platelet aggregation, amount of inflammatoryresponse cytokines which enhance thrombosis
• Similar findings of more recent study (JAMA. 2013;310(16):17111720)
Influenza ‘Nuts and Bolts’1
•Vaccination season: Soon as available to ~April
o Influenza
season unpredictable-can start Oct
o Immunity will last for almost all patients (no concern for waning
immunity for most patients)
o Late season vaccination important and underutilized
o LAIV can be safely used in MOST healthcare settings as
alternative to TIV2
•Egg allergy NO LONGER contraindication3
o Anaphylaxis
is EXCEEDINGLY rare [<10 documented cases]
o Flublok if concern
o OK to give egg-based if not history of severe anaphylaxis
• If vaccinated, should be observed ~30 minutes in office
1.
2.
Centers for Disease Control and Prevention. Inactivated Influenza Vaccine 2011-12. Available at: http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-flu.pdf
Talbot TR, et al. Infect Control Hosp Epidemiol. 2010;31:987-995.
Which vaccine for each patient?
•Patient
o Pregnant
women
o 67 y/o diabetic
o Prior hives with eggs
o 48 y/o smoker
o 58 y/o COPD
o 18 month child
• Vaccine
o Inactive(> 6 months)
o Trivalent ‘High dose’ inactive (65 +)
o Nasal ‘live’ vaccine (2-50)
o Intradermal vaccine (18-64)
o Quadrivalent inactive (>6 mo)
o Cell Culture; Recombinant (Flublok)
(>18)
o Cell Culture (canine cell; Flucelvax  )
(> 4)
25
Influenza and Pregnancy
• Pregnant woman at high risk for severe
complications and death
o
Cellular immune response diminished
o
o
o
Maternal hospitalization
Fetal malformation
Other illnesses
o
o
o
Several reports of 2nd MRSA infection
No approved vaccine for infants < 6 months of age
All care givers need to be free from possible transmission
to this vulnerable population
• Maternal influenza associated with
increased (Zaman et al. NEJM 2008)
• Prevention is best approach
• Newborns are at high risk for severe
complications
Benefits/Obligations of Influenza vaccine for
Healthcare providers
• As HCW we all have an obligation to protect our patients
Transmission may occur without illness
• May be asymptomatic carriers
• Infectious prior to onset of symptoms
o Studies show reduced transmission after vaccination
o
• Protection form acute illness
o For
H1N1 greatest morbidity and mortality is in ‘healthy’ individuals
aged 20-50.
• Protection of family members (especially if very young or
with medical conditions)
• Mandatory immunization of all HCW being implemented at
SUMMA
• Ohio House Bill 170: “prevent hospitals from mandating
the influenza vaccine”
77% of Influenza ‘asymptomatic’
•Flu Watch Study1
oCourse of influenza over 5 cohorts (2006-11)
oSerology; PCR; Weekly assessment for RTI
• Findings
o 77 %
o Only
appeared to asymptomatic
17% of PCR-confrimed infection sought medical attention
• “A large number of well individuals in the community make
a substantial contribution to transmission.”2
1. Hayward et al. Lancet Resp Med. 2014; 2: 445-54;
2. 2. Horby Lancet Resp Med. 2014; 2: 430
Centers for Disease Control and Prevention. 2010. Active Bacterial Core Surveillance Report,
Emerging Infections Program Network, Streptococcus pneumoniae, 2009.
http://www.cdc.gov/abcs/reports-findings/survreports/spneu09.pdf. Accessed February 3, 2011.
Pneumococcal Diseases causes more deaths per
year in US than Breast Cancer or Prostate Cancer
Xu. Et al. Deaths: Prelimanary data for 2007. Natl Vital Stat Rep. 2009; 58: 1-51
Pneumococcal Vaccines-adults
• 90 known serotypes of S. pneumoniae
• Pneumococcal polysaccharide vaccine (PPSV23)

Inactive vaccine; contains 23 serotypes which account for majority (75-80%) of clinical
disease.

Approved for use in adults of any age; ? Efficacy for pneumonia
• Pneumococcal conjugate vaccine (PCV13) approved for use
in adults age 50 and older

Inactive vaccine, conjugated with diptheria CRM 197 protein); 13 serotypes which
account for approx 45-50% of invasive disease

Approval from FDA announced December 30, 2011 for adults 50 years and older

Previously approved and recommended for use in children

CDC’s Advisory Committee on Immunization Practices (ACIP) recommends use for
patients who are immunocompromised
PNEUMOCOCCAL VACCINE
13 valent conjugated vaccine study for adults
CAPITA Study (Community Acquired Pneumonia Immunization
Trial in Adults)
• RCT trial in Netherlands
• Design
o 13 valent conjugate vaccine (same as pediatric vaccine)
o Placebo controlled (1:1); approx 85,000 subjects, > 65 years of
age, community dwelling
o Endpoints:
• Primary-prevention of CAP (serotype specific)
• Secondary-all cause CAP, colonization (2000 subjects),
mortality, bacteremia
•RESULTS:
o45%
reduction in vaccine typed non-bacteremic
pneumonia
o 75%
reduction in vaccine type Invasive disease
Bonten MJM et al. N Engl J Med 2015; 372: 1114–1125.
Strategies for sequential use of Conjugate and
Polysaccharide vaccine use in adults
• Conjugate vaccine more immunogenicity (higher antibody levels)
and can have booster effect
o 13
serogroups (accounts for approx 50% of invasive cases of pneumococcal
disease
• Polysaccharide vaccine less immunogenecity and NO booster
effect (may have hyporesponsiveness)
o But
has 23 serogroups (accounts for approx 89% of invasive cases)
• Give Conjugate first followed by polysaccharide for potentially
optimal effect
• If polysaccharide given initially wait one year to administer the
conjugate vaccine (reduce ? Hyporesponsiveness)
33
Source: Designed by National Foundation for Infectious Disease based on CDC recommendations; 2012
34
CDC Recommendations for aged > 65
Patient Scenarios
24 year with asthma has not previously received any
pneumococcal vaccine
28 year old woman with HIV infection received one dose
PPSV23 a year ago.
66 year old male, CHF, received PPSV23 age 55
Patient Scenarios
24 year with asthma has not previously received any
pneumococcal vaccine
PPSV23 now; PCV age 65 followed by PPSV 6-12 months
later
28 year old woman with HIV infection received one
dose PPSV23 a year ago.
Patient Scenarios
24 year with asthma has not previously received any
pneumococcal vaccine
PPSV23 now; PCV age 65 followed by PPSV 6-12 months later
28 year old woman with HIV infection received one dose
PPSV23 a year ago.
One dose PCV now (> one year since PPSV); 2nd dose PPSV23 age 32 (> 5 years since
PCV); 3rd dose PPSV age 65
Patient Scenarios
24 year with asthma has not previously received any
pneumococcal vaccine
PPSV23 now; PCV age 65 followed by PPSV 6-12 months later
28 year old woman with HIV infection received one dose
PPSV23 a year ago.
One dose PCV now (> one year since PPSV); 2nd dose PPSV23 age 32 (> 5 years since
PCV); 3rd dose PPSV age 65
66 year old male, CHF, received PPSV23 age 55
Patient Scenarios
24 year with asthma has not previously received any
pneumococcal vaccine
PPSV23 now; PCV age 65 followed by PPSV 6-12 months later
28 year old woman with HIV infection received one dose
PPSV23 a year ago.
One dose PCV now (> one year since PPSV); 2nd dose PPSV23 age 32 (> 5 years since
PCV); 3rd dose PPSV age 65
66 year old male, CHF, received PPSV23 age 55
One dose PCV13 now; PPSV23 one year later
Zoster Vaccine (Zostavax ™)
oLive
vaccine
• Not for pregnancy, immunocompromised (see next slide)
oFDA
approved in persons aged 50 years and older.
(CDC ≥ 60; evidence-supported)
oSingle SC injection within 30 minutes of
reconstitution
• In 38,000 patient study, reduced the incidence of shingles
by 51% in persons aged 60 years and older (less effective
in older patients)
• Incidence of postherpetic neuralgia less by 39%.
HZ
Vaccination
Silent
Reactivation?
VZV T Cells
VZV
Exposure
Vaccination Stimulates CMI
Zoster
Threshold
VZV
HZ
Age
CMI, cell-mediated immunity.
Adapted from Arvin A. N Engl J Med. 2005;352:2266-77.
Zoster Vaccine (Zostavax ™)
Most common questions
o What
if no history of chicken pox?
o What
if past zoster?
• OK to give
• Give after resolution of past episode; no specific time
o Is
it covered by Medicare
• Covered by Part D not Part B. Insurance payment varies by plan; To
be covered by ACA
o Should
I receive if around pregnant or immunosuppressed
persons?
• YES--not transmitted
oDo I need repeat dose?
• No recommendation at this time; but studies indicate waning
immunity after 7-11 years*; ? Redose
*Aging Clin Exp Res. 2015; 27: 757-65
Zoster Vaccine (Zostavax ™)
Immunocompromised pateints
oOptimal
to vaccinate ≥4 weeks prior to planned
immunosuppressive therapy.
oPatients with low-level immunosuppression (OK
to give per IDSA1)
• Prednisone ≤ 20 mg/day
• Methotrexate (≤ 0.4 mg/kg/wk)
• Azathrioprine (≤ 3 mg/kg/d)
o HIV
• One study found safe and effective if CD4# > 2002
1. Clin Infect Dis 2014; 58: e44; 2. Benson C et al. 19th Conference on Retroviruses and
Opportunistic Infections, Seattle WA, March 5-8 2012. Oral abstract #96)
Zoster: Special Consideration
•Simultaneous administration of pneumococcal
vaccine
o One study showed the average titer against varicella zoster virus
(VZV) was lower in persons who received zoster and PPSV at the
same visit compared to persons who received these vaccines 4
weeks apart
o However, a large study was subsequently conducted that
showed that zoster vaccine was equally effective at preventing
herpes zoster whether it was administered simultaneously with
PPSV or 4 weeks earlier
o CDC continues to recommend that HZV and PPSV be
administered at the same visit if the person is eligible for both
vaccines.
www.cdc.gov/vaccines/vpd-vac/shingles/hcpvaccination.htm&ei=LkhCVdGNM47SoAT46oGQAg&usg=AFQjCNFngsWk1AJGJ7j82iBjA2GCnYATw&bvm=bv.92189499,d.cGU (Mar 12, 2015)
Zoster vaccine in development:
subunit recombinant, adjuvant
• ZOE-50: associated with a risk of herpes zoster that was
97.2% lower than that associated with placebo in age 50
and older.
• 2nd trial (ZOE-70) for 70 + demonstrated 89% efficacy
and reduced PHN.
• Pooled analysis: 91% efficacy against zoster; 89%
against PHN
• 2 doses; AEs comparable.
1. Lal H, et al. N Engl J Med. 2015;372:2087-2096.
2. Cunningham AL, et al. N Engl J Med. 2016;375:1019-1032.Mar 12, 2015)
Meningococcal Serogroup B Vaccines
•Group B not in the Quadrivalent (A,C,Y,W)
•High-risk individuals
o Complement deficiencies,
o anatomic or functional asplenia,
o microbiologists routinely exposed
to N. meningitidis
isolates
o serogroup B meningococcal disease outbreak
•2 Vaccines:
oTrumenba™
• 3 doses for high-risk; 2 doses* (6 months apart) healthy
oBexsero™:
• 2 doses series
* ACIP Oct 2016
HPV Vaccine
• HPV 9-valent vaccine (Gardasil 9, Merck)
• The vaccine is indicated for females aged 9 to 26 years and
males aged 9 to 15 (26 high risk) years, and for cancers
caused by HPV types 6,11, 16, 18, 31, 33, 45, 52 and 58 and
for the prevention of genital warts caused by HPV type
• 97% effective in preventing cervical, vulvar and
vaginal cancers
49
The wars of the world: Saving lives through
vaccination
• Without the safe and effective vaccines that we too often
take for granted now, more than 300 million who lived full
and rewarding lives during the 20th century would have
died prematurely of a vaccine-preventable disease.
Compare this with the 160 million estimated to have been
killed in all wars combined during the same century. Stated
another way, vaccines saved twice as many lives as were
lost in war during the most destructive 100 years in human
history.
DW Kimberlin Inf Dis News. Aug 1, 2011
Summary
• Influenza vaccines
o Chose
based on age, allergy, preference
o ‘Flumist’ not recommended by ACIP 6/2016
• Adult Conjugate pneumococcal vaccine
o Now
with specific CDC recommendations
o Sequential administration with polysaccharide (give conjugate
first)
o CMS will pay for 2 vaccines (1 year apart)
• Zoster
o?
Of declining immunity
40-year-old woman from who has a history of
asthma, otherwise healthy. She has come to your
office for a health screen for a school cafeteria
job. Which Vaccines? Influenza, zoster,
pneumococcal
52
40-year-old woman from who has a history of
asthma, otherwise healthy. She has come to your
office for a health screen for a school cafeteria
job. Which Vaccines? Influenza, zoster,
pneumococcal
Influenza; and pneumococcal vaccines are appropriate.
She should also receive the annual influenza vaccine. Because of her asthma, she should
receive the inactivated vaccine [IV] rather than the live attenuated influenza vaccine
[LAIV]; In addition ACIP now prefers IV due to poor immunity of LAIV (2016). Her
asthma is an indication for her to receive polysaccharide pneumococcal vaccine.
53
65-year-old male has come to your office for a
physical examination. He has no medical records,
and reports that he has smoked for many years.
Initial evaluation reveals mild emphysema and
diabetes.
Which Vaccines?
Influenza, zoster, pneumococcal
54
65-year-old male has come to your office for a
physical examination. He has no medical records,
and reports that he has smoked for many years.
Initial evaluation reveals mild emphysema and
diabetes.
Which Vaccines?
Influenza, zoster, pneumococcal
His age (65 years), emphysema, and diabetes are
indications for all 3 vaccines. Influenza, pneumococcal
(13-conjugate followed in one year by the 23
polysaccharide), and Zoster. They can all be
administered at same visit.
55