Vaccination in Immunosuppressed Adults

Clinical Vaccinology

Update

The Melbourne Vaccine Education Centre

14 Sep 2018

Professor Katie Flanagan

Types of Immune Suppression to Consider

o Cancer and haematological malignancies

o Chronic diseases – diabetes, COPD,

autoimmune diseases

o Chronic infections – HIV

o Asplenia

o Physiological – pregnancy

o Stem Cell / Solid organ / bone marrow

transplant

o Drug induced

– Steroids

– Other immunosuppressive drugs –

methotrexate, azathioprine

– Cancer and haematological

malignancy treatments

o Immunotherapies

– Monoclonal antibodies

– Immune checkpoint inhibitors

General Ruleso Immune compromised persons are at increased risk

of morbidity and mortality from many VPDs

o Degree of immune compromise should be assessed to determine vaccination strategy

o Inactivated vaccines are generally safe in the immunocompromised adult but not always as immunogenic / efficacious

o Live vaccines are contraindicated in many immunocompromising situations due to risk of disseminated infection, in particular: – BCG is always contraindicated– Other live vaccines should not be given to those

with severe immunocompromise

o Severe immunocompromise includes active leukaemia, lymphoma, generalised malignancy, recent chemo (last 3 months), aplastic anaemia, GVHD, BMT or solid organ transplant in last 2 years, transplant recipients still taking immunosuppressives, high-dose corticosteroids

o Many vaccines can be given pre-emptively to people who anticipate immunocompromise in the future i.e. contemplating immunosuppressive therapy e.g. varicella zoster vaccine, pneumococcal vaccination

Influenza Vaccination

o Annual seasonal vaccination recommended for all immune compromised adults

o Should be given 2 doses at least 4 weeks apart the first time it is given

o In a pandemic situation 2 doses of vaccine may be given any season

General Rules

Cancer / Haematology Patients

Live vaccines

o Contraindicated if on immunosuppressive therapy or have poorly controlled malignancy

o Avoid when neutropaenic (<0.5x109/L)

o Wait until 3 months after treatment and confirmed remission

Inactivated Vaccines

o Give annual influenza (2 doses 1st time)

o Give any required inactivated vaccines

o Haematological malignancy patients (lymphoma, leukaemia, myeloma) should be given pneumococcal vaccination – 1 dose of 13 valent PCV then 2 doses of 23 valent PPV 8 weeks after PCV

Adult Cancer / Haematology Patients in Remission for >6 months

• Single dose dTpa

• Single dose MMR / IPV / HepB

(Check measles and rubella Abs 6-8 weeks after MMR and

revaccinate if non- seroconverter)

• Single dose 13vPCV then 2 doses 23vPPV

• Single dose Hib

Solid Organ Transplant

o Live vaccines contraindicated

o Inactivated vaccines safe but often delayed until 6 months post-treatment to maximiseimmunogenicity

Solid Organ Transplant

Vaccine Pre-Transplant Post-Transplant

(if not given before)

dTpa Yes Yes

IPV Yes Yes

HepA and HepB

Yes (depends on serostatus)

Yes (depends on serostatus)

13vPCV then 2 x 23vPPV

Yes Yes

MenACWY and MenB

Yes (if risk factors)

Yes (if risk factors)

Annual influenza

Yes Yes

MMR Yes No

Haematopoietic Stem Cell

Transplant

Protective immunity to VPDs partially or fully lost post HSCT, particularly first 6 months

Autologous HSCT patients recover immunity more quickly & don’t get GVHD

Haematopoietic Stem Cell Transplant

* Only if no ongoing GVHD and CMI has recovered

There is a role for donor immunisation with Hib, PCV, hepB and tetanus vaccines prior to harvest but rarely done

Vaccine Schedule

13vPCV 3 doses 6, 8, 12m post HSCT

23vPPV 1 dose 24m post HSCT

Hib / dTpa / IPV 3 doses 6, 8, 12m post HSCT

HepB 3 doses 6, 8, 12m post HSCTHigh dose formulation or dose in each arm each visit

4vMenCV and MenB 2 doses 6 and 8m

MMR * 24m - 1-2 doses (check Abs at 4wks)

Varicella * 24m - 2 doses 4wks apart if seronegative

20mg prednisolone is equivalent to:

• 16 mg methylpred

• 16mg triamcinolone

• 3.2mg dexamethasone

• 80mg hydrocortisone

Prednisolone Equivalent Dose

Duration Timing of Vaccination

<20mg / day Any Give any time

≥20mg / day < 14 days 1 month before or any time

after cessation

≥20mg / day ≥14 days 1 month before or at least 1 month after

cessation

Corticosteroids and Live Vaccines

Corticosteroids and DMARDS

If on <20mg prednisolone equivalent daily and low dose DMARDS then can still receive live vaccines

Low dose DMARDS:Drug Dose in 70kg adult

Methotrexate ≤0.4mg/kg/week = 28mg

Azathioprine ≤3mg/kg/day = 210mg

Mercaptopurine ≤1.5mg/kg/day= 105mg

Recent Blood Products /

Immunoglobulins

BCG, Zoster and Yellow Fever vaccination can be given any time before or after

blood products

Product Interval Before Live (MMR, MMRV, Varicella) Vaccination

Blood transfusion / washed RBCs 0 months

RBCs 3 months

Packed RBCs 5 months

Whole blood 6 months

NHIG for ITP / KawasakiNHIG for measles / hepA prophylaxis

8-11 months3-6 months

Plasma or platelets 7 months

RhD Ig (anti-D) 0 months

ZIG as varicella prophylaxis 5 months

HIV Infection

Live vaccines o Contraindicated if CD4 <200/μL (<15%), history of AIDS-defining illness, symptomatic HIV

infection

o BCG is always contraindicated

o Can give YF, MMR (if seronegative) and VZV (if seronegative) vaccines but NOT combined MMRV in asymptomatic HIV infection and those with CD4 ≥200/μL (15%)

o Zoster vaccine if ≥ 50 years and VZV IgG+ and CD4 ≥350/μL (some say ≥200/μL safe)

Inactivated Vaccineso Annual influenza

o Pneumococcal vaccination (1 x PCV13 + 2x PPV23)

o 4vMenCV and MenB – 2 doses of each

o HepA if non-immune

o HepB 4 double doses at 0, 1, 2 and 6m more immunogenic, check anti-HBs and repeat doses if <10mIU/mL

o 4vHPV – 3 doses @ 0, 2 and 6m. Females <45 yrs and males <26 yrs as per guidelines

Asplenia

At risk of fulminant bacterial infection particularly invasive pneumococcal disease

Go to Spleen Australia website for up-to-date advice https://spleen.org.au

Immunocompromised Travellers

o Yellow fever vaccine should be avoided in severe immunocompromise (travellers may need an exemption certificate)

o Do not give BCG

o Use the inactivated typhoid Vi polysaccharide vaccine not the live oral vaccine

Household Contacts

Vaccinate household & close contacts of

immune compromised

persons according to current

recommendations

In particular annual influenza

vaccination

Use of live vaccines in

contacts is highly recommended

Consider need for VZV (if ≥50

years) and pertussis-containing vaccines

Small risk of rotavirus vaccine

virus transmission to

the immune compromised

Name Target

Bimagrumab Type II activinrecptors

Alirocumab PCSK-9

Bocociziumab PCSK9

MABp1, Xilonix IL-1α

Gevokizumab IL-1β

Dupilumab IL-4Rα

Reslizumab IL-5

Benralizumab IL-5R

Sirukumab IL-6

Sarilumab /SA237 IL-6R subunit α

Lebrikizumab / Tralokinumab IL-13

Ixekizumab IL-17a

Brodalumab IL-17R

Tildrakizumab / Guselkumab IL-23 p19 subunit

Name Target

Actoxumab + Bezlotoxumab C diff enterotoxin A & B

Etrolizumab β7 integrin subunit

Tremelimumab CTLA4

MM-302 HER2

Patritumab HER3

MEDI-4736 / RG7446,MPDL3280A

PD-L1

Elotuzumab CD2

Inotuzumab ozogamicin / Moxetumomeb pasudotoc

CD22

Daratumumab CD38

Eculizumab Anti-complement C5

Rituximab / Ocrelizumab CD20

Alemtuzumab CD52

Epratuzumab CD22

Immunotherapies

Rituximab

o Depletes B cells (anti-CD20)

therefore prevents antibody

responses

o Different studies show differing

effects but generally vaccine Ab

responses (and CMI) impaired for up

to 6 months post administration

o Preferable to vaccinate prior to

commencing therapy if possible

Eculizumabo Indications: paroxysmal nocturnal

haemoglobinuria and atypical haemolytic uraemic syndrome

o Worlds most expensive drug, 2010 (£340,000/dose but now about $6,000)

o Associated with increased susceptibility to serious Neisseria meningitidis infection with a rate of 1% (Australian average rate: 1/100,000)

o Meningococcal vaccination recommended before starting treatment 4vMenV and MenBV 2 doses 8 weeks apart then check titres for response

o Check Ab titres annually if ongoing therapy and revaccinate if titres fall

o Antibiotic prophylaxis (PenV / erythromycn) also indicated

Prevents formation of the terminal complement complex C5b-9, by inhibiting the cleavage of C5-C5a

Immune Checkpoint Inhibitors

& Flu Vaccination

Influenza vaccination has been associated with increased incidents of myocarditis and death in people on checkpoint inhibitors

One study showed PD-1/PD-L1 inhibs caused >50% immune related AEs (rash, arthritis, encephalitis, colitis) (>25% had severe irAEs)

Australian immunisation handbook says to consult your oncologist for advice

They are likely to ask the ID physician / local vaccination specialist

Trials are ongoing to investigate this systematically

Pembrolizumab (PD-1 inhibitor), Nivolumab (PD-1 inhibitor) Atezolizumab (PD-L1 inhibitor), Ipilimumab (CTLA4 inhibitor)

Immune Checkpoint Inhibitors & Flu Vaccination

Can give if on single agent aPD-

1 or aPD-L1

Do not give flu vaccine within

6-8 wks of starting CTLA4 inhibs / combo therapy or 6-8

wks of stopping

Thank You