What are the differences between active and inactive (inactivated) vaccines in terms of protection and risk?

Active vs Inactive (Inactivated) Vaccines: Key Differences

Inactivated vaccines contain killed pathogens and cannot cause infection, making them safer for immunocompromised patients, while live attenuated vaccines contain weakened but living organisms that can replicate and may cause disease in vulnerable populations. 1

Fundamental Differences in Vaccine Composition

Inactivated Vaccines

• Contain killed or non-infectious viral/bacterial particles that cannot replicate in the host 1
• Include whole virion vaccines, subunit vaccines (containing only surface antigens like H and N), and split virion vaccines (broken viral structures with internal and surface antigens) 1
• Prepared through formalin inactivation and often adsorbed to aluminum hydroxide adjuvant 1
• Administered parenterally (intramuscularly) 1

Live Attenuated Vaccines

• Contain weakened but living organisms capable of limited replication 1
• Can be administered intranasally (e.g., live attenuated influenza vaccine) or parenterally 1
• Produce mild signs or symptoms related to the pathogen in some recipients 1

Protection and Immune Response Differences

Inactivated Vaccines

• Induce primarily antibody-mediated immunity with protective hemagglutinin-inhibiting (HI) titers of ≥1:40 in 70-100% of healthy adults 1
• Response is more limited in elderly patients (30-70% achieve protective titers) 1
• Do not interfere with immune responses to other inactivated vaccines or most live vaccines 1
• Require multiple doses and periodic boosters to maintain protective immunity 2
• Efficacy against serologically verified influenza: 68% (95% CI 49-79%) 1

Live Attenuated Vaccines

• Provide multifaceted immune response including local IgA, systemic antibody, and T-cell responses 3
• Do not achieve HI titers as high as inactivated vaccines but induce significantly higher local IgA in nasal mucosa 1
• Efficacy against serologically verified influenza: 48% (95% CI 24-64%) 1
• May provide broader cross-protection due to T-cell responses 3

Safety Profile and Risk Considerations

Inactivated Vaccines

• Remarkably safe with systemic reactions in <6% of vaccinees, similar to placebo rates 1
• Local reactions ("sore arm") occur in 15-20% vs 5-10% with placebo 1
• Cannot cause vaccine-associated disease even in immunocompromised patients 1, 4
• Safe during pregnancy and lactation 1
• Safe for patients with severe asthma and other chronic conditions 1

Live Attenuated Vaccines

• Local reactions (e.g., "runny nose") occur in ~40% vs 25% with placebo 1
• Can cause serious complications in immunocompromised patients including vaccine-associated paralytic poliomyelitis (VAPP), disseminated measles, and chronic rotavirus infection 1
• Contraindicated in patients with major antibody deficiencies, combined immunodeficiencies, and those on immunosuppressive therapy 1, 4
• Should not be administered to patients with IgA deficiency due to anaphylaxis risk 1

Critical Timing and Interaction Considerations

Inactivated Vaccines

• Can be administered simultaneously with other inactivated vaccines at separate anatomic sites 1, 5
• Can be given concurrently with live vaccines without timing restrictions 1
• Do not require spacing intervals between different inactivated vaccines 5

Live Attenuated Vaccines

• If not administered simultaneously with other live vaccines, a minimum 4-week interval must be maintained 1, 5
• Immunoglobulin (IG) can interfere with live vaccine response, requiring delays of >3 months for MMR and >5 months for varicella after IG administration 1
• Should not be given within 2 weeks after MMR or 3 weeks after varicella vaccine if IG is needed 1

Special Population Recommendations

Immunocompromised Patients

• All inactivated vaccines are recommended and safe for immunocompromised patients, including those on biologics like Tremfya 4
• Live vaccines are absolutely contraindicated in patients with major antibody deficiencies, combined immunodeficiencies, or on immunosuppressive therapy 1, 4
• Patients with partial DiGeorge syndrome require immune assessment (≥500 CD3 T cells/mm³, ≥200 CD8 T cells/mm³, normal mitogen response) before receiving live vaccines 1

Pregnant Women

• Inactivated vaccines can be administered at any time during pregnancy 5
• Live vaccines are generally avoided during pregnancy 1

Common Pitfalls to Avoid

• Never delay inactivated vaccination to space them out—they can be given simultaneously 5
• Do not assume live vaccines are safer because they seem more "natural"—they carry significant risks for vulnerable populations 1
• Do not mix vaccines in the same syringe unless specifically FDA-approved for mixing 5
• Avoid administering live vaccines to household contacts of severely immunocompromised patients (except most can be given safely) 4
• Do not use live attenuated influenza vaccine in immunocompromised patients when inactivated options are available 4