Live vs Killed (Inactivated) Vaccines - Microbiology

Note: The library does not contain "Apurva's Microbiology" specifically, but the following is drawn from the standard microbiology and immunology textbooks (Jawetz, Harrison's, Janeway's Immunobiology, Park's) that cover this topic in full. The content aligns closely with what Apurva's book teaches.

Classification of Vaccines

VACCINES
├── Live Vaccines (Attenuated)
├── Killed Vaccines (Inactivated)
└── Other: Subunit, Toxoid, Conjugate, mRNA, Viral vector

Live Attenuated Vaccines

• Serial passage in animal/cell cultures (usually a different species from the natural host)
• Accumulation of mutations in viral genome during repeated passaging
• Modern approach: rational attenuation by recombinant DNA engineering

• Multiplies in the host - mimics natural infection
• Stimulates both humoral (antibody) AND cell-mediated immunity (CMT)
• Induces secretory IgA at the portal of entry (mucosal immunity)
• CD8+ cytotoxic T cells are strongly activated (antigens processed intracellularly via MHC I)

1. Single dose usually sufficient (mimics natural infection)
2. Longer-lasting immunity (often lifelong)
3. No adjuvant needed
4. Stimulates both humoral and cell-mediated immunity
5. Induces local (mucosal) immunity - IgA at portal of entry
6. More closely mimics natural infection - greater effectiveness of protection

1. Risk of reversion to virulence (e.g., OPV - vaccine-associated paralytic polio, VAPP)
2. Contraindicated in immunocompromised hosts (may cause severe infection)
3. Contraindicated in pregnancy
4. Limited shelf life - requires cold chain (thermolabile)
5. May contain unrecognized adventitious (contaminant) agents
6. Difficult to achieve the desired level of attenuation

Killed (Inactivated) Vaccines

• Virus grown in culture (e.g., monkey kidney cells, human diploid fibroblasts, embryonated eggs)
• Inactivated by mild formalin treatment (most common), heat, or beta-propiolactone
• Purified to minimize host-cell components

• Cannot replicate - does NOT mimic natural infection
• Antigens are NOT processed via MHC Class I pathway
• Mainly stimulates humoral (antibody) immunity
• Weak cell-mediated immunity - CD8 T-cell responses rely on cross-presentation
• No mucosal (IgA) immunity produced at portal of entry

1. No risk of reversion to virulence - safest type
2. Safe in immunocompromised patients and pregnancy
3. Can be made when no acceptable attenuated virus is available
4. Stable, longer shelf life, easier to store
5. Multiple antigens can be included in one preparation

1. Multiple doses needed (boosters required)
2. Shorter duration of immunity
3. Adjuvant often required to enhance immune response
4. Poor/no cell-mediated response
5. No local (mucosal) immunity
6. May cause occasional hypersensitivity to subsequent infection
7. Lower effectiveness compared to live vaccines

Comparison Table (Jawetz - Table 30-9)

Classic Exam Comparison: OPV vs IPV (Polio)

Key Exam Points (Frequently Tested)

• "Live vaccines mimic natural infection" - most important distinguishing concept
• Only live vaccines induce mucosal IgA and CMI
• Only live vaccines can cause VAPP (vaccine-associated paralytic poliomyelitis)
• BCG is the only live bacterial vaccine routinely used
• Smallpox vaccine (vaccinia) is a live vaccine that uses a related (not attenuated) virus
• Cold chain is mandatory for live vaccines (thermolabile)
• Killed vaccines need adjuvants (aluminum salts - alum) to boost response
• OPV is banned/replaced by IPV in polio eradication programs due to VAPP risk