Immunization of

immunocompromised persons
SARA ABOLGHASEMI
FACULTY MEMBER OF SBMU, ID SPECIALIST ,FELLOWSHIP OF
IMMUNOCOMPROMISED PATIENTS
Introduction

 The safety and effectiveness of vaccines in immunocompromised persons are

determined by the type of immunodeficiency and degree of
immunosuppression.

 Each immunocompromised person is different and presents unique

considerations regarding immunization.
Inactivated vaccines

 Inactivated vaccines may generally be administered to immunocompromised

people if indicated.

 The antigens in the vaccine cannot replicate and there is no increase in the risk
of vaccine-associated adverse events.

 However, the magnitude and duration of vaccine-induced immunity are often

reduced.
 Live attenuated vaccines

 People who are severely immunocompromised or in whom immune status is uncertain

should not receive live vaccines because of the risk of disease caused by the vaccine
strains.

 In less severely immunocompromised people, the benefits of vaccination with routinely

recommended live vaccines may outweigh risks.

 Before giving an immunocompromised person a live vaccine, a physician with expertise in

immunodeficiency should be consulted.
Common Inactived vaccines:

DTaP/Tdap/Td
Hepatitis B
HPV
Influenza(IIV, RIV)
Pneumococcal
Zoster (Shingrix)
Hepatitis A
Polio(IPV)
Meningococcal
Hib
Common live attenuated vaccines

 Measles, Mumps and Rubella

 Varicella (Chickenpox)
 MMRV
 Zoster (Zostavax)
 Polio (OPV)
 Influenza(LAIV)
 Rotavirus
 Yellow fever
Pneumococcal Vaccine

 Polysaccharide: PPSV23
Not immunogenic in younger than 2y and immuncompromised people

 Conjugated: PCV13, PCV15, PCV20

Immunogenic in younger than 2y and immuncompromised people
Adult dosage if indicated:
PCV13
8weeks later : PPSV23
5 years later : PPSV23 (immunocompromised)
Children Younger than 2 Years Old

 CDC recommends PCV13 or PCV15 for all infants as a series of 4 doses.

 Give 1 dose at 2 months, 4 months, 6 months, and 12 through 15 months.

 Children 2 through 4 Years Old without Certain Medical
Conditions

 CDC recommends PCV13 or PCV15 vaccination for children 2 through 4 years old who
are unvaccinated or received an incomplete pneumococcal conjugate vaccine (either
PCV13 or PCV15) series. PCV13 and PCV15 can be used interchangeably.
 Children 2 through 5 Years Old with Certain
Medical Conditions

 For a child with any of these conditions:

 Cerebrospinal fluid leak
 Chronic heart disease, particularly cyanotic congenital heart disease and cardiac failure
 Chronic lung disease, including asthma if treated with prolonged high-dose oral
corticosteroid therapy
 Cochlear implant
 Diabetes mellitus
CDC recommends :

 Give 2 doses of a pneumococcal conjugate vaccine (either PCV13 or PCV15) if they are
unvaccinated or received an incomplete pneumococcal conjugate vaccine series with <3
doses before 24 months of age. Give the second dose at least 8 weeks after the first.
 Give 1 dose of PCV13 or PCV15 if they received 3 doses of a pneumococcal conjugate
vaccine before 12 months but have not received their fourth booster dose.
 Give 1 dose of PPSV23 at least 8 weeks after the pneumococcal conjugate vaccine series
is complete.
Adults 65 Years or Older

 For adults 65 years or older who have not previously

received any pneumococcal vaccine, CDC recommends
you:
 Give 1 dose of PCV13 or PCV20.
 If PCV15 is used, this should be followed by a dose of PPSV23 at least one year later. The
minimum interval is 8 weeks and can be considered in adults with an immunocompromising
condition, cochlear implant, or cerebrospinal fluid leak.
 If PCV20 is used, a dose of PPSV23 is NOT indicated.
 Zoster vaccine

 Live vaccine: Zostavax

Herpes zoster vaccine (Zostavax [Merck & Co., Inc.]) was licensed in 2006 and
recommended by the Advisory Committee on Immunization Practices (ACIP) in 2008 for
prevention of herpes zoster (shingles) and its complications among adults aged ≥60 years,
The Food and Drug Administration (FDA) approved the use of Zostavax in 2011 for adults
aged 50 through 59 years
 Zoster Vaccine Recombinant(RZV)
Adjuvanted (Shingrix, GlaxoSmithKline [GSK]) is a 2-dose (0.5 mL each) subunit vaccine
licensed in the United States for prevention of herpes zoster for adults aged ≥50 years by the Food
and Drug Administration (FDA) and recommended for immunocompetent adults aged ≥50 years
On October 20, 2021, ACIP recommended 2 doses of RZV for the prevention of herpes zoster and
related complications in adults aged ≥19 years who are or will be immunodeficient or
immunosuppressed because of disease or therapy. RZV is the first herpes zoster vaccine approved
for use in immunocompromised persons
 RZV

 Two RZV doses are necessary, regardless of previous history of herpes zoster or
previous receipt of zoster vaccine live. The second RZV dose should typically be
given 2–6 months after the first;
 For persons who are or will be immunodeficient or immunosuppressed and who
would benefit from a shorter vaccination schedule, the second dose can be
administered 1–2 months after the first
 RZV may be administered to patients who previously received varicella vaccine.
RZV is not a live virus vaccine; therefore, RZV may be administered while patients
are taking antiviral medications.
Influenza vaccine types

Include:
 Inactivated influenza vaccines [IIV4],
 Recombinant influenza vaccine [RIV4],
 live attenuated influenza vaccine (LAIV4).
For many years, flu vaccines were designed to protect against three different
flu viruses: an influenza A(H1N1) virus, an influenza A(H3N2) virus and one
influenza B virus, even though there are two different lineages of B viruses
that circulate during most seasons.(Yamagata, Victoria) Adding a B virus
from the second lineage was done to give broader protection against
circulating flu viruses.
 General principles

· Immunize at the time when maximum immune response can be anticipated:

 Immunize prior to any planned immunosuppression, if possible.

 Delay immunization if the immunodeficiency is transient (if this can be done
safely because exposure is unlikely).
 Stop or reduce immunosuppression to permit better vaccine response, if
appropriate
 General principles

 Consider the immunization environment broadly:

Vaccinate family members and other close contacts when appropriate.

Strongly encourage up-to-date vaccinations, including annual influenza vaccination, for all
healthcare workers providing care to immunocompromised people
General principles

• Avoid live vaccines unless:

 Immunosuppression is mild and data are available to support their use.

 The risk of natural infection is greater than the risk of immunization.

 Malignant hematologic disorders

 In general, inactivated vaccines should be administered to people with malignant

hematologic disorders according to routine immunization schedules, although
response may be sub-optimal.

 Immunization should be given at least 2 weeks prior to the start of

immunosuppressive therapy or when immunosuppressive therapy is at the lowest
level unless the risk of imminent exposure to the pathogen is high.
Malignant hematologic disorders

 Hepatitis B vaccine should be given at double the routine dose and using a 3 or 4
dose schedule.

 HPV vaccine should be given following routine age indications but using a 3 dose
schedule regardless of age.

 Doses of any a vaccine received while on immunosuppressive therapy should be

repeated once no longer immune suppressed, unless an adequate antibody
response can be demonstrated.
 Malignant hematologic disorders

 Individuals with malignant hematologic neoplasms should also receive conjugate

pneumococcal vaccine (regardless of age)

 Pneumococcal polysaccharide vaccine if age 2 years or more

 For infants 6 months of age or older, annual immunization with inactivated

influenza vaccine is also recommended
Malignant hematologic disorders:
Live attenuated vaccines

 Immunodeficiency due to lymphomas, leukemias of any type, or other malignant neoplasms affecting the bone
marrow or lymphatic systems and in people undergoing immunosuppressive chemotherapy or radiotherapy
treatment for these conditions.

 In general, if the cancer is in remission and chemotherapy and/or radiotherapy have been completed for at least 3
months, and T cell function is normal, the person is no longer considered immunocompromised and live
vaccines may be given.

 Live vaccines should be deferred for at least 12 months after therapy with anti B-cell antibody
 Non-hematologic malignant solid tumours:
Inactivated vaccines

 Inactivated vaccines should be administered to people with malignant solid tumours

according to routine immunization schedules.

 Immunization should be given at least 2 weeks prior to the start of immunosuppressive

therapy.
 Doses of any vaccine received while on immunosuppressive therapy should be repeated
once no longer immune suppressed unless an adequate antibody response can be
demonstrated.
Non-hematologic malignant solid tumours:
Inactivated vaccines

 In addition, pneumococcal conjugate vaccine (regardless of age) and

polysaccharide vaccine (if age 2 years or more) should be given because of
increased susceptibility to invasive pneumococcal disease.

 For infants 6 months of age or older, annual immunization with inactivated

influenza vaccine is also recommended.
Non-hematologic malignant solid tumours:
Live attenuated vaccines

 Live vaccines are contraindicated in people undergoing

immunosuppressive treatment for any malignant solid tumour.

 In general, if chemotherapy has been completed for at least 3

months and the cancer is in remission, the person is no longer
considered immunocompromised.
 Hematopoietic stem cell transplantation (HSCT): autologous or
allogeneic

 Virtually all HSCT recipients experience a prolonged period of immune suppression following
transplantation.
 Antibody titres to vaccine-preventable diseases decrease after allogeneic or autologous HSCT.
 Duration of immune suppression varies, depending on type of transplant (allogeneic or autologous),
stem cell source, stem cell manipulation and post-transplant complications.
 Allogeneic HSCT recipients experience profound immune suppression in the post-transplant period,
with recovery of the immune system approximately 1-2 years after HSCT.
 However, this recovery is delayed in the presence of immunosuppressive medication and chronic graft-
versus-host disease (cGVHD).
 Pre-HSCT immunization

 If time permits, careful consideration must be given to the pre-transplant immunization status
of the HSCT candidate.
 All routine inactivated vaccines should be given as appropriate for age.
 In addition, conjugate pneumococcal vaccine (regardless of age) and polysaccharide
pneumococcal vaccine (if age 2 years or more) should be given if not previously received.
 If the transplant is planned during the influenza season, inactivated influenza vaccine should
be given.
 Recipient

 Inactivated vaccines should be given at least 2 weeks prior to onset of the pre-transplant
conditioning regimen.

 Live vaccines should not be given within 4 weeks of the start of conditioning.

 BCG should not be given at any time to those with a condition that will likely
eventually require HSCT. There is a theoretical risk of reactivation post-transplant
 If transplantation is urgent, it should not be delayed to facilitate donor or recipient
vaccination.
DONOR

 Donor vaccination may improve responses of the HSCT recipient to some

vaccines; however, due to logistical and ethical issues it is often not feasible
 As a minimum, the donor should have received all routine age-appropriate
vaccines including routine boosters, COVID-19 vaccines, and influenza
vaccine if stem cell collection is to occur during the influenza season.
 Inactivated vaccines should be given at least 2 weeks prior to stem cell
collection. Live parenteral vaccines are contraindicated within 4 weeks of stem
cell collection
Post-HSCT immunization

 HSCT recipients should be viewed as "never immunized“.

 HSCT recipients respond poorly to polysaccharide vaccines, such as

pneumococcal polysaccharide 23-valent vaccine.

 All routine inactivated vaccines should be given (or repeated) for

HSCT recipients generally beginning 6 months.
 Post-transplant pneumococcal conjugate vaccine may be given beginning at 3 to 6 months post-
transplant.
 Inactivated influenza vaccine may be given beginning at 4 to 6 months post-transplant.
 Pneumococcal conjugate vaccine and Hib vaccine should be given regardless of age.
 Those 2 years of age or older should receive pneumococcal polysaccharide vaccine at 12 to 18
months post-transplant (6 to 12 months after the last dose of pneumococcal conjugate vaccine) if no
GVHD.
 Hepatitis B vaccine should be given at double the dose used in the routine 3-dose schedule.

 HPV vaccine should be given using a 3-dose schedule, regardless of age.

 For those with risk factors for invasive meningococcal disease (e.g., functional hyposplenia),
quadrivalent conjugate meningococcal is recommended and meningococcal B vaccine should
be considered.
Live attenuated vaccines

 MMR and univalent varicella vaccines may be considered 24 months or more post-transplant
provided there is no evidence of chronic GVHD, immunosuppression has been discontinued for at
least 3 months, and the person is considered immunocompetent by a transplant specialist.

 Yellow fever vaccine may be given if the above criteria are met and travel to an area with risk of
yellow fever acquisition cannot be avoided.
 Other live vaccines are contraindicated.

 Live herpes zoster vaccine is not recommended post HSCT.

Zoster

 Recombinant inactivated zoster vaccine may be considered in

immunocompromised adults ≥ 50 years of age on a case by case basis.

 Data on the use in immunocompromised individuals is limited, but based on the

burden of zoster illness in this population and the general safety of inactivated
vaccines, the benefits of vaccination are expected to outweigh the risks.
Solid organ transplantation

 All transplant candidates should be up to date on their routine vaccines as per national
guidelines.
 Inactivated vaccines should be given at least 2 weeks prior to transplant where possible for an
adequate immune response.
 Live‐attenuated vaccines should be given at least 4 weeks prior to transplant to ensure that
vaccine‐related viral replication has resolved prior to transplant.
 In the post‐transplant setting, inactivated vaccines can be administered starting at 3 ‐6 months
post‐transplant
 Except influenza vaccine which can be given as early as 1 month post ‐transplant
Influenza vaccine

 Earlier studies have shown that vaccine given in the first 6 month post‐
transplant is poorly immunogenic;

 however, a recent study indicates that vaccination as early as 1 month post‐

transplant is safe and immunogenic.

 Guidelines by the Kidney Disease Improving Global Outcomes (KDIGO)

group also recommend to give influenza vaccine starting at one month
post‐transplant.
 Hepatitis B vaccine

 Various formulations of Hepatitis B vaccine are available and vary in the amount of surface
antigen (10, 20, 40 μg).

 a 3‐dose or 4‐dose vaccine series should ideally be given prior to transplantation as early in the
course of disease as possible if the transplant candidate is non ‐immune with anti ‐HBs titers <10
IU/mL.

 An adjuvanted hepatitis B vaccine (HepB‐CpG with 20 μg antigen) has also recently become
available for persons ≥18 years of age and is given as a two ‐dose series at 0 and 1 month.
 Higher dose of vaccine (40 μg) is recommended for those with end ‐stage renal disease. Post ‐
transplant patients may also benefit from higher doses.
 Hepatitis B surface antibody titers should be checked approximately 4 weeks after
the last dose of vaccine to document protective titers.

 Serial hepatitis B surface antibody titers should be assessed periodically if the patient
has ongoing risk for hepatitis B exposure or is traveling to a high‐risk area.

 Revaccination can be done in non‐responders or those with waning immunity (anti ‐

HBs <10 IU/mL) by either administering a complete series again using the high ‐dose
(40 μg) vaccine or giving one dose and checking anti‐HBs.
Pneumococcal vaccine

 Protein‐conjugated vaccines induce a T‐cell dependent response and may produce

antibodies of higher avidity and also lead to formation of memory B cells while
PPSV23 elicits a T‐cell independent response.

 Recommendations for pneumococcal vaccination of immunocompromised adults

suggest a single dose of PCV13 followed 8 weeks later by PPSV23. A second
PPSV23 should be repeated 5 years after the first dose
 Herpes zoster vaccine

 Herpes zoster vaccines are now available in two formulations: (a)a live ‐attenuated zoster
vaccine (LZV) and (b) a recombinant subunit zoster vaccine (RZV).
 Due to the very high efficacy of RZV (~97%) in this age group, RZV is currently
recommended over LZV for prevention of shingles.

 In general, LZV should be avoided post‐transplant whether or not the transplant recipient
is VZV seropositive.
 An immunogenicity and safety study of two‐dose RZV in adult kidney transplant
recipients age ≥18 years has been performed
household and close contacts

 It is preferred that household and close contacts be vaccinated against measles,

mumps, rubella, and varicella to prevent the .

 It is preferable that HCW and close contacts receive inactivated influenza

vaccine
During or after immunosuppressive therapy

 Generally a period of at least 3 months should elapse between therapy cessation

and the administration of inactivated vaccines (if possible, to ensure maximum
immunogenicity) or live vaccines (to reduce the risk of disease caused by the
vaccine strain).

 This interval may vary with the type and intensity of treatment, underlying disease,
or urgency of vaccination if vaccines are needed for post-exposure or outbreak
management.
 For example, whereas immunization can occur as early as 4 weeks following
discontinuation of long term high-dose systemic steroid therapy,
 a longer interval of 6 to 12 months or more may be required in case of therapy
with rituximab (or other monoclonal anti-B cell antibody) and some other
biological response modifiers.
 Recipients of CAR T cell therapy directed against lymphocytes should be
regarded as “never immunized” and managed as HSCT recipients are.
 The primary series (initial or repeat) of inactivated vaccines, including COVID-
19 vaccines which should be initiated 3 to 6 months after CAR T cell therapy.
 Live vaccines may be given immediately on discontinuation of high dose steroid
therapy if duration was less than 14 days.
 Corticosteroid therapy is not a contraindication to immunization with live vaccines
when steroid therapy is short-term (i.e., less than 14 days); or low-to-moderate dose
(prednisone equivalent of less than 2 mg/kg/day or less than 20 mg/day if weight > 10
kg);
 For recipients of therapy with long term effects on the immune system, such as CAR
T directed against lymphocytes, anti-B cell antibody, and some other biological
response modifiers, live vaccines should not be given until adequate immune
reconstitution has been confirmed by an expert.
THANK YOU