What are examples of live vaccines, such as the measles, mumps, and rubella (MMR) vaccine, and which patients should not receive them due to compromised immune systems, such as Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) or chemotherapy?

Live Vaccines: Types and Contraindications

Live vaccines include MMR (measles, mumps, rubella), varicella (chickenpox), zoster (shingles), rotavirus, LAIV (intranasal influenza), yellow fever, BCG (tuberculosis), oral typhoid (Ty21a), and oral polio (no longer routinely used in most countries). 1

Complete List of Live Vaccines

Live Viral Vaccines

• MMR (Measles, Mumps, Rubella): Combined vaccine providing protection against three viral diseases 1
• Varicella (Chickenpox): Single-antigen vaccine for prevention of primary varicella infection 1
• Zoster vaccines:
  • Live attenuated (Zostavax) for shingles prevention in adults ≥60 years 1
  • Note: Recombinant zoster vaccine (Shingrix) is NOT a live vaccine and is preferred for immunocompromised patients 1
• Rotavirus: Oral vaccine for prevention of severe diarrheal disease in infants 1
• LAIV (Live Attenuated Influenza Vaccine): Intranasal spray formulation 1
• Yellow fever: For travelers to endemic areas 1
• Oral polio (OPV): No longer routinely used in UK and many countries due to risk of vaccine-associated paralysis 1, 2

Live Bacterial Vaccines

• BCG (Bacille Calmette-Guérin): For tuberculosis prevention in high-risk populations 1
• Oral typhoid (Ty21a): Oral vaccine for typhoid fever prevention 1

Absolute Contraindications for Live Vaccines

Live vaccines are absolutely contraindicated in patients receiving immunosuppressive therapy, defined as prednisolone ≥20 mg/day for ≥2 weeks, thiopurines, methotrexate, biologic therapies, or JAK inhibitors. 1

Specific Patient Populations Who Must NOT Receive Live Vaccines

Severe Immunodeficiency States

• Severe Combined Immunodeficiency (SCID): All live vaccines contraindicated 1
• Complete DiGeorge syndrome: All live vaccines contraindicated 1, 2
• HIV/AIDS with severe immunosuppression: CD4 count <200 cells/mm³ in adults or CD4 percentage <15% in children 1, 3
• Active malignancy on immunosuppressive therapy: All live vaccines contraindicated 2

Patients on Immunosuppressive Medications

• Corticosteroids: Prednisolone ≥20 mg/day or equivalent for ≥2 weeks 1
• Biologic therapies: Anti-TNF agents, anti-integrins, anti-IL agents, JAK inhibitors 1
• Conventional immunomodulators: Azathioprine >3 mg/kg/day, mercaptopurine >1.5 mg/kg/day, methotrexate >25 mg/week 1

Other High-Risk Situations

• Pregnancy: All live vaccines generally contraindicated due to theoretical fetal risk 2
• Significant protein-calorie malnutrition: All live vaccines contraindicated 1

Critical Timing Considerations

Live vaccines must be administered ≥4 weeks before starting immunosuppressive therapy, and immunosuppressive therapy should be withheld for 4 weeks after live vaccine administration. 1

Timing Guidelines

• Before starting immunosuppression: Administer live vaccines ≥4 weeks prior to initiating therapy 1
• After stopping immunosuppression: Wait ≥3 months after discontinuing immunosuppressive therapy before administering live vaccines 1
• Between multiple live vaccines: Either give on same day OR separate by ≥4 weeks 2
• Infants exposed to biologics in utero: Avoid live vaccines for 12 months after birth (exception: rotavirus may be given on schedule after in utero anti-TNF exposure) 1

Special Circumstances Where Live Vaccines MAY Be Considered

Low-Level Immunosuppression

Certain live vaccines may be considered in patients on low-level immunosuppression, defined as prednisolone ≤20 mg/day for >14 days, either alone or combined with low-dose non-biologic immunomodulators (methotrexate ≤25 mg/week, azathioprine ≤3 mg/kg/day, or mercaptopurine ≤1.5 mg/kg/day). 1

• Zoster vaccine (live): May be administered to patients aged 70-79 years on low-level immunosuppression 1
• This exception does NOT apply to patients on biologic therapies 1

HIV-Infected Patients with Adequate Immune Function

• MMR vaccine: Can be given to HIV-infected adults with CD4 ≥200 cells/mm³ or children with CD4 percentage ≥15% 1, 3
• Varicella vaccine: Can be given to HIV-infected adults with CD4 ≥200 cells/mm³ or children aged 1-13 years with CD4 percentage ≥15% 1, 3
• Yellow fever vaccine: May be considered in asymptomatic HIV-infected adults with CD4 ≥200 cells/mm³ or children aged 9 months-5 years with CD4 percentage ≥15% if travel to endemic area cannot be avoided 1

Specific Primary Immunodeficiencies

• Complement deficiencies: Can typically receive all routine vaccines including live vaccines 2
• Phagocytic function defects (chronic granulomatous disease, leukocyte adhesion defects): Should avoid live bacterial vaccines (BCG, oral typhoid) but can receive live viral vaccines 1, 2, 3
• Partial DiGeorge syndrome: Recent data suggest risk may be low in some situations 1

Household Contact Vaccination

Household members of immunocompromised patients SHOULD receive all age-appropriate live vaccines including MMR, varicella, rotavirus (for infants), and zoster to create a protective barrier. 1, 3

Important Exceptions

• LAIV (intranasal influenza): Should NOT be given to household contacts of HSCT recipients within 2 months post-transplant, patients with GVHD, or patients with SCID 1
• If LAIV is administered to household contacts of these high-risk patients, avoid contact for 7 days 1
• Oral polio vaccine: Should NOT be given to household contacts due to viral shedding risk 2

Common Pitfalls to Avoid

• Do not confuse recombinant zoster vaccine (Shingrix) with live zoster vaccine (Zostavax): Shingrix is NOT live and is safe for immunocompromised patients 1
• Do not give live vaccines to patients receiving IVIG: Circulating antibodies will inactivate MMR and varicella vaccines; delay vaccination 8 months after standard IVIG dose (300-800 mg/kg) or 11 months after high-dose (2 g/kg) 1
• Do not assume all immunodeficiencies require avoidance of all live vaccines: Patients with isolated B-cell deficiencies or complement deficiencies may tolerate live vaccines differently than those with T-cell defects 1, 2
• Do not forget to check varicella immunity before starting immunosuppression: Administer varicella vaccine ≥4 weeks before therapy if seronegative 1