Immunization

AngstMay 2020

Kelly Ford,MD

Assistant Professor Harvard Medical School

Beth Israel Deaconess Medical Center

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Goal: Discuss evolving vaccine

recommendations

� Objectives

� Influenza vaccine efficacy

� Pneumococcal complexity

� Meningococcal changes

� Zoster challenges

� Hepatitis B special indications

� HPV expanding recommendations

� Tdap emphasis in pregnancy

� Asplenic vaccine protocols

� Virtual vaccination

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Resources

� CDC/Annals/JAMA/MMWR

� National recommendations

� VIS for patients

� ACIP

� Advisory board for vaccines

� Immunization Action Coalition

� Standing orders

� Patient and provider resources

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Georgia

� Doc, I want the best flu vaccine and I want it as soon as

possible.

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Issues of Concern

� Maximal influenza vaccine efficacy 59%

� Much lower than desired, especially in high risk individuals

� Discrepancy between publicity and efficacy.

� Recommendations not evidence based

� Limited benefit noted for children >7 years

� Limited safety and efficacy data for pregnant women

� Lack of benefit

� Greater vaccination of elders with limited mortality benefit

� Limited documented benefit in high risk groups

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High Dose Influenza Vaccine

� 4 times the antigen dose as standard dose vaccine

� Trivavlent only (2 A serotypes and 1 B)

� Approved only for those 65 and older

� Cost up to 3X, usually covered by Medicare

� 24% higher antibody response

� Lower rate of hospitalizations

� No proven mortality benefit to date.

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Pregnancy and Influenza

Not clear that pregnancy increases risk for contracting

influenza.

Vaccine decreases risk of influenza 24-50% infection.

Most data for increased risk for influenza complications in

pregnancy comes from pandemics

In pandemic pregnancy increases risk for more severe

disease and death from influenza.

First trimester influenza linked to increased congenital

anomaly(OR 2.0). Antipyretics attenuate this risk.

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Egg Allergy Kerfuffle

� Unified statements by allergy associations:

� "Vaccine providers and screening questionnaires do not need to ask about the egg allergy status of recipients of influenza vaccine.”

� Anaphylaxis to eggs

� 1,000’s of patients, including with anaphylaxis, have safely received influenza vaccines manufactured with albumin

� Observation in office could be considered

� Egg free options

� Cell culture

� Recombinant tri / quadravalent vaccine

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Antigen Match

� Greater valency (H1,H2, H3) (H5, H9 pandemic)

� Hemagglutinin head of virus

� Neuraminidase nonneutralizing. Limit spread

� Consider sites not involved with rapid antigenic drift

� Highly conserved

� Viral stalk

� Alternative antigen matches

� Membrane proteins expressed on infected cells

� The Compelling Need for Game-Changing Influenza Vaccines. 10/2012

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Immune Boosters

� Adjuvants

� Oil in water, aluminum salts

� Induce local inflammatory response

� Boost innate immune response

� Increased local reactions

� Short term and long term safety

� Unknown efficacy

� Serial vaccinations

� Boostering effect

� Immune stimulants

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Vaccine Effectiveness

� Antigen Match

� Immune response in individual

� Herd immunity

� Persistence of immunity

� Effectiveness in high risk individuals

� Seasonal and pandemic coverage

� MMWR June 5, 2015 64(21);583-590

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Durability of response

� Avoid annual vaccination

� Requires ability to offer wide antigen coverage or conserved

sites

� Requires robust and sustained immune response

� Reduced cost

� Greater effectiveness

� Sustained response especially helpful in elders

� Annual vaccination least effective in elders

� Declining response to vaccines/antigens

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What does this mean to you or

your patient?

� Understand true expected efficacy of the influenza

vaccine—59% at best

� Limit exposure, especially for high risk individuals

� With exposure consider prophylaxis for high risk

individuals.

� Reduce modifiable risk factors (smoking, obesity)

� Advocate for change/improvement

� Participate in trials and research

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Jackson

� 65 year old man with moderately severe COPD is sent

up from pulmonary clinic for his 5th pneumococcal immunization.

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Prevention of Invasive

Pneumococcal Disease

� Polysaccharide 23 valency vaccine

� Vaccinate all persons 65 and older ONE time

� New additions 2010 CDC

� Active smoking status

� Asthma

� No need to routinely vaccinate Alaskans and American

Indians

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Medical Indications for ONE

Pneumococcal Vaccine < 65

� Asthma

� Smoking

� Diabetes

� Chronic Disease

� Heart (not HTN)

� Lung

� Liver (including ETOH overuse)

� CSF leak/cochlear implant

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Robert, a 28 year old

photographer, with HIV

� Would he benefit from one or two pneumococcal

vaccines?

� Which pneumococcal vaccines?

� What order of immunization?COPYRIGHT

Medical Indications for TWO

Pneumococcal Vaccines <65

Asplenia (functional or anatomic)

� Immunocompromised state(congenital/acquired)

� Complement, B cell, T cell deficiency

� HIV

� Long term suppression (ie transplant)

� Chronic renal failure/Nephrotic syndrome

� Heme/Lymphatic malignancy

� Generalized malignancy

� Vaccines should be spaced by 5 years

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Conjugate Pneumococcal Vaccine� 13 valency vaccine previously given only to children

� Higher, longer antibody titre

� Lower valency

� New recommendations:

� Apslenia(functional or anatomic)

� Immunocompromised status

***NO LONGER ROUTINELY RECOMMENDED >65***

NEJM 2015:372;1114-25

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Timing

� If no pneumococcal vaccine ever given:

� PCV13 first

� PPSV23 2 or more months later

� If prior PPSV23 given:

� PCV13 12 or more months later

Medicare will cover both vaccines, but only if delivery

separated by 11 or more months.

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Eilzabeth

� A 75 year woman quips to her PCP that she could have

purchased a whole pig for the price of the zoster vaccine and she would have been better off!

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Varicella Choices

� Varicella

� Intended for primary/childhood series

� Two doses

� ZVL

� Live inactivated, cannot be used in immunosuppression

� Declining efficacy with age

RZV

� Recombinant, safe, but untested in immunosuppression

� Higher efficacy

� More local reactions

� Supply chain issues

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Adjuvant Zoster Subunit Vaccine

� NEJM 2015:372:2087-96.

� Phase 3 study 15,000 people 50 to > 70 in 18 countries

� Two dose vaccine(> 2 months apart)

� Recombinant subunit vaccine

� AS01 adjuvant (Promotes CD4 T cell humoral response)

� 85% rate of local reactions/significant 9.5%

� 66% systemic reactions(placebo 29%)

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Recombinant Vaccine Efficacy

� 97% (CI 94-99% P< 0.001) efficacy in all people > 50

� No decreased response with age. Recommended > 50

� No need to check titre before vaccination

� Not tested in immunocompromised individuals

� Can be given after zoster outbreak.

� Private insurers cover cost more highly in clinic

� Part D medicare covers at pharmacy as “medication.”

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Juan

� 35 year old man continues to suffer recurrent bouts of

uremia. What vaccines do you consider as you make arrangements for fistula placement?

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Hepatitis B Vaccine

� Prior to dialysis initiation at least two doses of Hepatitis B

� Accelerated schedule possible (0,7,14,180 days)

� Immunocompromised patients are recommended to receive higher antigen vaccine and/or more doses

� 40ug(recombivax) or 2 doses of standard 20ug (engerix)

� 0, 1,2,6 or 0,1,6 months

� Annual screen for surface Ab to determine if booster needed

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Hepatitis B

� New recommendation to vaccinate all diabetics < 60 due to blood exposure issues.

� Health care workers (check titres), blood exposure

� MSM (also Hep A)

� Heterosexual intimacy with more than one partner

� Chronic liver disease (also Hep A)

� HIV positive persons, STI

� Injection drug use

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WeiWei

� This 50 year old Chinese man comes to clinic after

recent imprisonment for artistic expression. He does not have any medical records. He thinks he may have been

given one or more doses of the hepatitis B vaccine.

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Hepatitis B Vaccine

� Incarceration is another indication for the Hepatitis B

vaccine

� Two different three dose vaccines each can be given

over 6 months-variable complicated schedules.

� Newer vaccine that provides immunization for both

Hepatitis A and B in the same vaccine.

� Vaccines given late may offer same benefit, but not early

� If no antibody response repeat whole series.

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New Hepatitis B Vaccine

Approved for those 18 and older

� 2 doses (separate by 1 month)

� Efficacy 90-100% (current 70-90%)

� No greater rate of adverse reaction

� Not approved in pregnancy

� Not interchangeable with other HBV vaccines

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Tracey

“Everyone I have ever slept with”

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HPV Hype

� Bivalent (16,18) approved only for females

� Quadravalent (6,11,16,18) and 9 valency vaccines approved for males and females

� Age range 9-26 females and males with target 11 year children

� NEW permissive recommendation to age 45

� Coverage of HPV serotypes inducing cervical cancer

� 2 and 4 valency 65%, 9 valency 80%

� 4 and 9 valency vaccines cover 90% of serotypes genital warts

� Pregnancy is precaution for vaccine. HCG not recommended r

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HPV Ambiguity

� Public fear and dis/mistrust of vaccine

� Higher rate of syncope with vaccine, but within range for

adolescent vaccines

� Lower uptake than expected—50% in some communities

� Reduced, but documented benefit in women with prior sexual exposure, abnormal pap smears, or known HPV

infections.

� Shared decision making in men/women aged 27-45.

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Keith

� This young artist comes inquiring about ways to reduce

risk in his dynamic personal life.

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Male HPV

� Reduction in male genital warts, penile cancer, anal

cancer, and cervical cancer

� Vaccination of males and females aids in reduction of

cervical cancer risk

� Vaccination now recommended for all males 9-26.

� Immunocompromised state, HIV, higher benefit

� MSM

� Improved insurance coverage with this recommendation

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Vaccines for MSM

� New risk category for CDC vaccine recommendations

� Hepatitis A

� Hepatitis B

� HPVCOPYRIGHT

Andrew

� Healthy 70 year old grandfather. His daughter in law has

sent him to get a vaccine to protect the baby.

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Td or Tdap Goals

� Prevent tetanus, especially with wounds

� Continue eradication of diptheria

� Reduce prevalence and mortality of pertussis, especially in neonates who carry highest risk

� Minimize vaccination requirementsCOPYRIGHT

Tdap Timing in Adulthood

� FDA FINALLY approved Tdap for serial use

� One Tdap booster in early adulthood due to waning

pertussis immunity and high prevalence.

� Td OR Tdap every 10 years

� 5 year frequency for concerning wounds

� Tdap recommended for all adults surrounding an infant

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Sophia

� This 25 year old artist comes to see you interested in the

whopping cough vaccine for her baby.

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Pertussis in Infants

� Highest mortality from pertussis for infants 0-3 months

who do not achieve fully immunity until 12 months

� High maternal antibodies can pass to neonate- 90%

coverage in infants for 2-3 months

� Higher maternal antibody levels persist for < 12 months

� Recommendation for vaccination with Tdap at 27 to 36

weeks with EACH pregnancy to protect infant

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Local Reactions

� Common event for Td/Tdap vaccines

� Anaphylaxis—minutes/in the office

� Arthus reaction 4-12 hours

� Allergic reaction

� Local reaction(not allergic)

� Cellulitis

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Td/Tdap Bottom Line

� Td OK for anybody

� Every 10 years Td or Tdap

� Tdap booster in young adulthood waning immunity

� Tdap for each pregnancy 27-36 weeks ideal

� Avoid Tdap in pregnancy < 20 weeks

� Wound frequency 5 years

� Local reactions are troublesome

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Mick

� 55 year old Irish artist and passionate cyclist loses his

spleen in a biking accident.

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Splenectomy Recommendations

� Ideally all vaccines 14 days prior to surgery

� Secondarily, 14 or more days post splenectomy

� One time Haemophilus Influenza B vaccine

� Meningococcal vaccines X2 then every 5 years

� Pneumococcal series (4 vaccines)

� Annual influenza vaccine

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Pneumococcal Coverage

� Pneumococcal polysaccharide vaccine

� Three total doses

� One dose surrounding initial asplenic state

� Repeat in 5 years

� One dose at 65 or 5 years after second dose

� Pneumococcal conjugate vaccine

� One time dose

� First vaccine followed 8 weeks later by polysaccharide

� If second, twelve or more months after polysaccharide

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Meningococcal Recommendations

� Initial series 2010 ACIP Recommendations

� 2 vaccines separated by 8 weeks

Meningococcal conjugate vaccine A, C, W, Y

Higher titres

More durable response

If ongoing risk repeat every 5 years

Same recommendations for those with HIV, complement

deficiency

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Meningococcal B Vaccine

� Two available vaccine preparations (2 or 3 doses). Not

interchangeable vaccines

� Adolescents 16-23, discussion pros/cons

� Recommended for those at increased risk,

immunosuppression

� Group B meningitis outbreak

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Virtual Vaccination

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Really? Vaccination?

� Push on for primary/pediatric series

� Pros/cons

� Time frame—impending HD?

� Patient fears

� Relative benefit (Tdap)

� Pharmacy possibilities

� Rx for correct vaccine

� Documentation woes

� Zero zoster

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SARS CoV-2 Vaccine

� Over 30 submissions for vaccine candidates—TPP

� Experimental work on animals underway

� Early phase 1 trials started.

� Virus binds to the ACE-2 receptor in the lung

� ACE-2 receptors increased in elders

� 80% homology with SARS-CoV amino acid sequence

� Platforms for Ebola, Zika, SARS/MERS could be used

� Only one major pharmaceutical company involved

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What are we looking for in a

SARS-CoV-2 Vaccine?

� # 1 Efficacy

� Not sufficient to be effective on young healthy patients

� Three high risk subgroups include:

� HCW, people over 60, people with chronic medical conditions

� # 2 Safety

� Rush for vaccine should not short cut process, reviews

� Immunopotentiation (whole virus/complete spike)

� Risk for more severe different disease, increased infectivity

� # 3 Mass production

� Can smaller firms scale up rapidly? millions of doses?

� Stockpile

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Vaccine Candidates

� Whole virus

� Inherent immunogenicity inactivated or killed

� Recombinant Protein Subunit Vaccine

� Immune response against spike protein prevents docking on

ACE-2 receptor.

� Faster production

� Needs adjuvant for efficacy

� Nucleic Acid Vaccine (DNA or RNA)

� No currently licensed vaccine similar

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Caution with Live Vaccines

� MMR, Varicella, ZVL, Nasal Influenza, oral typhoid

� Do not give in pregnancy

� Do not give with immunocompromised state

� Caution in 11 months following blood product transfusion

� Labeling, decision support, cross checks with “risky

vaccines” MMR, Varicella, Zoster

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Avoid in Pregnancy

� MMR (28 days no conception)

� Live attenuated/nasal influenza

� Varicella, Zoster

� Tdap < 20 weeks

� HPV

� Oral Typhoid

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Vaccine Choices

� Influenza

� IM, ID, IN

� Standard, high antigen

� Valency

� Td vs Tdap

� Pregnancy < 20 weeks, target 27 to 36 weeks

� Pneumococcal (PCV13 vs PPSV23)

� Meningococcal ( MenB, MCV A,C,W,Y)

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Vaccine Recap

� Influenza-choices, 60% efficacy, new direction needed

� Pneumococcal-polysaccharide and conjugate vaccines

� Meningococcal vaccine teens, at risk, immune deficient

� Zoster-New subunit vaccine efficacy > 95%

� Hepatitis B-diabetics, high dose renal failure, new vaccines

� HPV-men and women < 27 target, up to 45

� Td/Tdap-focus on pregnant women 27-36 weeks

� Asplenia-2 meningococcal vaccines, 4 doses of pneumococcal vaccine, HIB, Influenza

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