Vaccination in immunocompromised adults - Slideset by Professor Filippo Ansaldi

Immunocompromised persons vary:

Nature of immunodeficiency

Degree of immunosuppression

Response to immunization

Susceptibility to infection

Vaccine safety and vaccine efficacy

Vaccine benefit

Recommandations

Pro Cons

Heterogeneous group of immunodeficiency

Wide spectrum of clinical manifestations

Caused by >200 known single gene mutations leading to defects of innate

and/or adaptive immunity

Predisposition to autoimmunity and malignancies

Increased susceptibility to infections that influences the final prognosis

Combined immunodeficiencies with/without

associated or syndromic features

Predominantly antibody deficiencies (50%)

Diseases of immune dysregulation

Congenital defects of phagocyte number,

function, or both

Defects in innate immunity

Autoinflammatory disorders

Complement deficiencies

1 10 100

Incidence

Prevalence Europe: 41,401- 638,015

North America: 19,464- 299,947

Worldwide: 390,546- 6,018,593

Europe: 76,148

North America: 35,799

Worldwide: 718,326

5.6/100,000*

*The number of PID patients are estimated from the

prevalence datafor Australian registry

**The number of PID patients are estimated from the

prevalence reported for the US telephone survey

Age (y) Incidence World N (%) Europe (%) North America (%)

0-4 21.9 139,886 (18.8) 8,757 (10.4) 5,183 (13.1)

5-14 7.2 87,338 (11.8) 5,356 (6.4) 3,223 (8.2)

15-24 9.7 117,679 (15.9) 8,862 (10.5) 4,652 (11.8)

25-49 6.8 166,499 (22.4) 18,182 (21.6) 8,014 (20.3)

50-74 15.2 189,772 (25.6) 31,901 (37.9) 13,941 (35.3)

>75 12.7 40,762 (5.5) 11,173 (13.3) 4,438 (11.2)

86/100,000**

Bousfiha AA et al., 2013

Joshi A et al., 2011

10.2-10.4/100,000*y

Principi N & Esposito S, 2014

Type of PID Type of infectious

risk

Recommended vaccines Contraindicated vaccines

Phagocytic cell defects Bacterial and fungal

infections

Inactivated vaccines Live attenuated bacterial vaccines in

chronic granulomatous disease.

Live attenuated viral and bacterial

vaccines in leucocyte adhesion deficiency

and cytotoxic granule-release defect.

Complement deficiencies Bacterial infections All (probably effective) None

TLR and IL-12/IFN-

gamma signalling

pathway defects.

Viral infections (HSV)

Bacterial infections(Non-tuberculous

Mycobacteria, non-

typhoidal Salmonella)

Inactivated vaccines Live attenuated should be given after

evaluating immune system efficiency

Minor antibody

deficiencies (IgA

deficiency, IgG subclass

deficiency, SPAD, ATS)

Viral infections(Enterovirus)

Bacterial infections

All None

Major antibody

deficiencies (X-linked

agammaglobulinemia,

CVI, ataxia-telangiectasia

DiGeorge syndrome,

Wiskott–Aldrich

syndrome)

Viral, bacterial and

fungal infections

Inactivated influenza

vaccines and vaccines

based on bacterial

polysaccharides

Live attenuated vaccines (except to

MMRV in ptz with CD4 ≥ 500 cells/ L,

CD8 ≥200 cells/ L and a normal mitogen

response or with CD4 cells/L ≥25%)

Natural Age Extremes: Prematury and Old age

Acquired Human immunodeficiency virus (HIV) infection/AIDS

Cancer (particularly hematopoietic and lymphoid malignancies)

Metabolic diseases

Malnutrition

Asplenia

Protein-losing enteropathy

…

Iatrogenic Radiation

Immunosuppressive medication therapy (cyclosporine,

dacarbazine, amphotericin B, antithyroid agents, chloramphenicol,

chloroquine, interferons, penicillamine, corticosteroid, many

cancer chemotherapy agents, etc.)

Organ transplantations

…

Heterogeneous group of immunodeficiency

Wide spectrum of clinical manifestations

Both the innate and the adaptive immunodeficiencies affect

Increased morbidity and mortality

Continously increasing

Eibl MM & Wolf HM, 2015; IDSA, 2014

Type of SID Type of

infectious risk


HIV Viral, bacterial

and fungal

infections

All Live attenuated vaccines if CD4<200 cells/μl

Hematological

and solid

malignancies

Viral, bacterial

and fungal

infections

All inactivated vaccines.

Live attenuated vaccines in low-

level ID ptz.

Live attenuated vaccines during chemotherapy

HSCT Viral, bacterial

and fungal

infections

All inactivated vaccines. MMR-ZV up to 24mo post transplant, up to 3mo

after immunosuppressive therapy in chronic

GVHD.

Solid organ

tranplant

Viral, bacterial

and fungal

infections



level ID ptz.

Live attenuated vaccines.

Immunosuppre

ssive therapy

in AI diseases

Viral, bacterial

and fungal

infections



level immunosuppression: to be

considered.

Live attenuated vaccines in high-level

immunosuppressed pt (4ws before to 4ws after

high-dose cortcosteroid therapy; 4ws before to

3mo after biological modifiers therapy).

Asplenia Bacterial

infections

All LAIV

Eibl MM & Wolf HM, 2015; IDSA, 2014

Type of SID Type of

infectious risk


HIV Viral, bacterial

and fungal

infections

All Live attenuated vaccines if CD4<200 cells/μl

Hematological

and solid

malignancies

Viral, bacterial

and fungal

infections



level ID ptz.

Live attenuated vaccines during chemotherapy

HSCT Viral, bacterial

and fungal

infections

All inactivated vaccines. MMR-ZV up to 24mo post transplant, up to 3mo

after immunosuppressive therapy in chronic

GVHD.

Solid organ

tranplant

Viral, bacterial

and fungal

infections



level ID ptz.

Live attenuated vaccines.

Immunosuppre

ssive therapy

in AI diseases

Viral, bacterial

and fungal

infections



level immunosuppression: to be

considered.

Live attenuated vaccines in high-level

immunosuppressed ptz (4ws before to 4ws after

high-dose cortcosteroid therapy; 4ws before to

3mo after biological modifiers therapy).

Asplenia Bacterial

infections

All LAIV

High Level Immunosuppression

Combined PID

Receiving cancer chemotherapy

Within 2 months from SOT

Within 6 months from HSCT

HIV infection, CD4 T cell<200 cell/mm3

Receiving daily corticosteroid, dose>20 mg

of prednisone for >14 days

Receiving biologic immune modulators,

such as TNF-Alpha-blockers, rituximab, …

IDSA 2014

Paucity of efficacy and safety data

Undervaccination

Pro Cons

«The primary care clinician and

respective specialist following the patient

are responsible for assuring vaccination

of immunocompromised patients»

[IDSA, 2014]

Indications Schedule Recommendation,

Strength of

Recommendation and

Quality of Evidence

All immunocompromised subjects Inactivated influenza vaccines (IIV)

Single dose annualy

LAIV should not be administered

in immunocompromised patients

Recommended (S, M)

HSCT patients Pre-HSCT

Post- HSCT

IIV single dose annualy

IIV single dose annualy 6 months

after (4mo after if there is a

community outbreak of influenza)

Usual (S, L)

Recommended (S, M)

Administration (S, VL)

SOT recipients Pretransplant

Starting 2-6 mo Posttransplant


Single dose annualy (Including the

first 2-month post-transplant period)

Usual (S, M)

Usual (S, M)

Administration (S, L)

HIV Low-level or no immunosuppression

High-level immunosuppression

IIV single dose annually


Usual (S, H)

Usual (S, H) Some cases of increase

in viremia and a decrease of CD4+

cells, not clinical symptoms.

Asplenia and sickle cell disease IIV single dose annually Usual (S, M)

Chronic Inflammatory diseases on

immunosuppressive medications

IIV single dose annually Usual (S, M)

Solid or hematologic cancer

Prior to or During Chemotherapy

Starting ≥3 mo Postchemotherapy and ≥6 mo

Post Anti–B-Cell Antibodies



Usual (S,L-M)

Usual (S,M)

W=weak; L=low; VL=very low; M=moderate; S=strongh; H=high


Strength of

Recommendation and

Quality of Evidence

All immunocompromised subjects Inactivated influenza vaccines (IIV)

Single dose annualy

LAIV should not be administered

in immunocompromised patients

Recommended (S, M)


Post- HSCT


IIV single dose annualy 6 months

after (4mo after if there is a

community outbreak of influenza)

Usual (S, L)

Recommended (S, M)

Administration (S, VL)




Single dose annualy (Including the

first 2-month post-transplant period)

Usual (S, M)

Usual (S, M)


HIV infected patients

Low-level or no immunosuppression




Usual (S, H)

Usual (S, H) Some cases of increase

in viremia and a decrease of CD4+

cells, not clinical symptoms.

Asplenic patients and sickle cell disease IIV single dose annually Usual (S, M)

Chronic Inflammatory diseases or


IIV single dose annually Usual (S, M)



Starting ≥3 mo Postchemotherapy and ≥6 mo

Post Anti–B-Cell Antibodies



Usual (S,L-M)

Usual (S,M)


• Contraindicated in subjects receiving anti–B-cell antibodies such as rituximab or

alemtuzumab or intensive chemotherapy such as for induction or consolidation

chemotherapy for acute leukemia (W, L).

• Vaccines administered while receiving cancer chemotherapy should not be considered valid

doses (S, L).

• Administration of indicated inactivated vaccines 2 or more weeks prior to chemotherapy is

preferred.

• Inactivated influenza vaccine can be administered ≤3 months after chemotherapy, but

response rate may be low.


Strength of

Recommendation and

Quality of Evidence

Primary immunodeficiency disorders (classic pathway

(C1, C2, C3, C4), alternate pathway, or severeMBL

deficiency who are PCV13 naïve)

End-stage heart, kidney, liver or lung disease

Chronic inflammatory diseases on immunosuppressive

medications

First dose of PCV13, PPV23 > 8 weeks

after PCV13 and a second dose of

PPV23 5 years later.

For patients who were immunized with

PPv23, PCV13 should be administered

>1 year after the last PPv23 dose.

Well tolerated,

Recommended (S, L-M))


Post- HSCT 3 doses PCV13 after 3-6 months (2

months interval)

1 dose PPv23 12 months after

transplantation

Recommended (S,VL-L)

Recommended (S, L)



PCV13 >4weeks prior to transplant

If not administered pretransplant.

Recommended (S, VL)

Recommended (S, VL)

Asplenia and sickle cell disease PCV13 2 weeks after splenectomy or 2

weeks before surgery

Recommended (S, VL)

GVHD patients, after resolution A dose of PCV13 and a dose of PPV23

after at least 8 weeks

Recommended



A dose of PCV13 and a dose of PPSV23

after at least 8 weeks.

Recommended (S, L)

Recommended (S, VL)



Starting ≥3 mo Postchemotherapy and ≥6 mo Post

Anti–B-Cell Antibodies

Recommended (S,VL-L)

Usual (S, L)


Indications Schedule Recommendation, Strength of

Recommendation and

Quality of Evidence

PID (Leukocyte adhesion deficiency,

Defects of cytotoxic granule release such as

Chediak-Higashi syndrome, defects of IFN

alpha or gamma production)

Controindicated (S, M)

HSCT (patients without evidence of MMR

immunity, no GVHD and no immunosuppres. drug)

Pre-HSCT

Post-HSCT At least 2 y after transplant, 2-doses

schedule of MMR at least 3 mo interval

Usual (S,VL)

Contraindicated (S; L) (not

administered combined with V)



Usual (S, M)

Contraindicated (S, L)



2-doses schedule of MMR at least 3 mo

interval (not administered combined

with V vaccine)

Usual (W, VL)

Contraindicated (S, M)

Asplenic patients and sickle cell disease Usual (S, M)

Chronic Inflammatory diseases on immunosup.

Medications Planned Immunosuppression

Low-high level Immunosuppression

Usual (S, M)

Contraindicated (W, VL)





3 mo after chemoterapy, 2-doses



Usual (S, L)

Patients receiving anti-B-cell antibodies After at least 6 mo, 2-doses schedule of

MMR at least 3 mo interval

Should receive vaccine (not




Recommendation and

Quality of Evidence

PID (Leukocyte adhesion deficiency,

Defects of cytotoxic granule release such as

Chediak-Higashi syndrome, defects of IFN

alpha or gamma production)

Controindicated (S, M)

HSCT (patients without evidence of MMR

immunity, no GVHD and no immunosuppres. drug)

Pre-HSCT

Post-HSCT At least 2 y after transplant, 2-doses


Usual (S,VL)

Contraindicated (S; L) (not




Usual (S, M)




2-doses schedule of MMR at least 3 mo

interval (not administered combined

with V vaccine)

Usual (W, VL)


Asplenic patients and sickle cell disease Usual (S, M)

Chronic Inflammatory diseases on immunosup.

Medications Planned Immunosuppression


Usual (S, M)






3 mo after chemoterapy, 2-doses



Usual (S, L)

Patients receiving anti-B-cell antibodies After at least 6 mo, 2-doses schedule of

MMR at least 3 mo interval

Should receive vaccine (not



Chemiotherapy4 weeks 3 months 3 monthsX X X

Anti-B-cell Ab4 weeks 6 months 3 monthsX X X

HSCT4 weeks Administer, at 24 months, if

- Seronegative

- Not immunosuppr.

- No GVHD

X X

SOT4 weeksX X

U – patient not current with recommendation

for immunocompetent individuals


Recommendation and

Quality of Evidence

All immunocompromised patients Not licensed Potential risk of severe disease

PID disorder without defective T-cell–mediated

immunity

2-dose schedule separated by a

3-month interval

Recommended (not administered

combined with MMR vaccine)

HSCT

Pre-HSCT

Post-HSCT

See later

See later

Usual (S, L)


SOT recipients

Pretransplant


See later

See later

Usual (S, L)


Immunosuppressive therapy

Planned Immunosuppression


See later

See later

Usual (S, M)

Contraindicated (W-S, VL-M)



Usual (S, VL)


Asplenia and sickle cell disease Usual (S, M)





Starting at 3 month


Usual (W, VL)



Recommendation and

Quality of Evidence

All immunocompromised patients Not licensed Potential risk of severe disease

PID disorder without defective T-cell–mediated

immunity

2-dose schedule separated by a

3-month interval

Recommended (not administered

combined with MMR vaccine)

HSCT

Pre-HSCT

Post-HSCT

See later

See later

Usual (S, L)


SOT recipients

Pretransplant


See later

See later

Usual (S, L)





See later

See later

Usual (S, M)




Usual (S, VL)







Starting at 3 month


Usual (W, VL)


Chemiotherapy4 weeks 3 months 2 monthsX X X

Anti-B-cell Ab4 weeks 6 months 2 monthsX X X

HSCT4 weeks Administer, at 24 months, if

- Seronegative

- Not immunosuppr.

- No GVHD

X X

SOT4 weeksX X

U – patient not current with recommendation

for immunocompetent individuals


Recommendation and

Quality of Evidence

All immunocompromised subjects Not licensed Potential risk of severe disease

Subject aged > 50 years 4 weeks before beginning

immunosuppressive therapy

Should be considered

50-59 years (W, L)

>60 years (S, L)

PID

HSCT

Pre-HSCT

Post-HSCT

See later

See later

Usual (S, L)


SOT recipients

Pretransplant


See later

See later

Usual (S, L)


HIV








See later

See later

Usual (S, L)







Starting at 3 mo

Contraindicated (S, VL)

Usual (W, VL)



Recommendation and

Quality of Evidence

All immunocompromised subjects Not licensed Potential risk of severe disease

Subject aged > 50 years 4 weeks before beginning

immunosuppressive therapy

Should be considered

50-59 years (W, L)

>60 years (S, L)

PID

HSCT

Pre-HSCT

Post-HSCT

See later

See later

Usual (S, L)


SOT recipients

Pretransplant


See later

See later

Usual (S, L)





See later

See later

Usual (S, L)


Patients with leukemia in remission and who have not

received chemoterapy or radiation

3 months after therapy Recommended

HIV










Starting at 3 mo

Contraindicated (S, VL)

Usual (W, VL)


Chemiotherapy4 weeks 3 monthsX X

Anti-B-cell Ab4 weeks 6 monthsX X

HSCT4 weeksX

SOT4 weeksX

U – patient not current with recommendation for

immunocompetent individuals


Recommendation and

Quality of Evidence

All immunocompromised

subjects

A single dose


In asymptomatic HIV-infected

adults with CD4 T-cell lymphocyte

count ≥200 cells/mm³

who travel to an endemic area

A single dose Administration (W, L)


Vaccines Indications and Schedule Recommendation, Strength of

Recommendation and

Quality of Evidence

Inactivated vaccines Usual (S, H)

Influenza vaccine

TIV and QIV

LAIV

Single dose IM/intradermal (ID) 0.5 mL annually

Healthy, not pregnant, 2-49 years

Contact with HSCT recipiens within 2 months after transplant

or with GVHD and contact with severe combined immune

deficiency (If administered, contact between the

immunocompromised patient and household member should

be avoided for 7days)

Administer (S, H)

Administer (S, L)


Measles, mumps and

rubella

Administer (S, M)

Rotavirus vaccine Highly immunocompromised pts, avoid handling diasper

of vaccinated infants for 4 weeks

Administer (S, L)

Varicella Vaccine If skin lesion develop, avoid close contact with

immunocompromised persons

Administer (S, M)

Zoster Vaccine >60 years

If skin lesion develop, avoid close contact with

immunocompromised persons

Administer (S, M)

OPV Contraindicated ( S, M)


PID and SID subjects are largely undervaccinated

In PID and SID, vaccination may

improve quality of life and prognosis

reduce infectious complications and be life saving

Raising awareness of the importance of vaccination to

physicians is needed

New studies based on the level of immune suppression

and vaccine effectiveness may provide more results


Recommendation and

Quality of Evidence

HSCT

Pre-HSCT

Post-HSCT

The patient will be not immunosuppressed

and there will be an interval of ≥4 weeks

prior to transplant

Usual (S, L)


(administer if varicella seronegative ≥24

months after transplant, no GVHD is present,

and the patient is not receiving

immunosuppressive medication. 2 doses

should be administered. S, L)

SOT recipients

Pretransplant


Usual (S, L)



immunosup. medications



≥4 weeks prior to immunosup. medications Usual (S, M)




Strength of

Recommendation and

Quality of Evidence

HIV Low-level or no

immunosuppression


2-doses Usual (S, M)

Usual (S, M)



Starting ≥3 mo Postchemotherapy and ≥6 mo Post Anti–B-Cell

Antibodies

2-doses

Usual (W, L)

Usual (S, VL)

Chronic inflammatory diseases on Immunosuppressive

Medications

2-doses Usual (S, L-M)

Asplenia and sickle cell disease 2-doses Usual (S, M)

HSCT

Pre-HSCT

Post-HSCT

2 doses

2 doses; 6 mo

Usual (S, VL)

Recommended (W, L)



2 doses pre-transplantation or 6

months after transplantation

Recommended (S, M)

Recommended (S, M



Recommendation and

Quality of Evidence

Chronic inflammatory diseases on immunosuppressive

medications

3-doses Usual (S, L-M)

Asplenia and sickle cell disease 3-doses Usual (S, M)





3-doses, 2 or 3 wks

3-doses

Usual (W, VL)

Recommended (S, VL)

HSCT

Pre-HSCT

Post-HSCT

3 doses

3 doses, 6 mo

Usual (S, L)

Recommended (S, M)



3 doses schedule pre-

transplantation or 6 months after

transplantation

Recommended (S, M)

Recommended (S, M)



High-dose HBV vaccine (40 µg) Recommended (S, M)

Recommended (S, M)



Recommendation and

Quality of Evidence

Asplenia and sickle cell disease Recommended (W, L)


Post- HSC 3-doses schedule, 6-12 months

after transplantation

Usual (S, M)

Recommended (S, M)





Usual (W, L)

usual (S, M)



Usual (S, M)

Usual (S, M)



Usual (S, L-M)



Recommendation and

Quality of Evidence

Patients with primary complement deficiencies MCV4 2-doses <55 y, booster

dose every 5y

MPV4 >55y if they have

not received MCV4, booster dose

every 5y



Asplenia and sickle cell disease 2 weeks before splenectomy

MCV4 <55y second dose after 5y

MPV4 >55y

Recommended (S, L)



Usual (S, L-M)





Usual (W, L)

Usual (S, L)



Usual (S, M)

Usual (S, M)


Indications Schedule Recommendation

Strength of

Recommendation and

Quality of Evidence


Post- HSCT 3-doses schedule with DTaP, 6

months after HSCT (dTap should

be considered as a booster

dose).

Usual (S, L)

Recommended for the innitial

vaccination (S, L)





dTap, 3 mo after chemoterapy

dTap, after at least 6 mo anti-B-

cell antibodies

Usual (W, L)

Recommended (W, VL)

Recommended (S, M)

Chronic Inflammatory diseases on immunosuppressive

medications

dTap as booster dose Usual (S, L-M)



dTap as booster dose

dTap as booster dose

Usual (S, M)

Usual if not completed pretraplant

(S, M)



dTap as booster dose Usual (S, VL)

Usual (S, VL)




Recommendation and

Quality of Evidence

In all immunocompromised subjects for disease or

medication

3 doses at 0,1-2 and 6 mo Recommended (S, L)



HPV4 3 doses 0, 2, 6 mo

HPV4 3 doses 0, 2, 6 mo

Usual (S, VL)

Usual (S, VL)





3 doses at 0,1-2 and 6 mo


Usual (W, VL)

Usual (S, VL)


Post- HSCT


6mo after transplant 3 doses at 0,1-2

and 6 mo

Usual (S, VL)

Usual (W, VL)



3 doses at 0,1-2

3 doses at 0,1-2

Usual (S, L-M)

Usual (S, L-M)



3 doses at 0,1-2 Usual (S, VL-M)

Asplenia and sickle cell disease 3 doses at 0,1-2 Usual (S, M)


PID and SID subjects are largely undervaccinated

Vaccination may improve quality of live and prognosis

of PID

Vaccination could reduce infectious complications and

be life saving in SID patients

Raising awareness of the importance of vaccination to

physicians is needed

New studies based on the level of immune suppression

and vaccine effectiveness may provide more results

Evaluation and monitoring of the immune response

could improve treatment decisions, reduce

complications of disease, hospitalization and costs.

Health & Medicine

Vaccination in immunocompromised adults - Slideset by Professor Filippo Ansaldi