Immunoprophylaxis microbiology
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Immunoprophylaxis in Microbiology
Immunoprophylaxis refers to the prevention of infectious disease through induction or transfer of immunity. It encompasses two broad strategies: active immunization (vaccines) and passive immunization (antibodies).
1. Definitions
| Term | Definition |
|---|---|
| Vaccination | The act of introducing a vaccine into the body to induce protection from a specific disease |
| Immunization | The process by which a person becomes resistant to a disease, usually by vaccination (or passively) |
| Immunoprophylaxis | Prevention of disease by inducing or transferring immune protection before exposure occurs |
Vaccines are defined as inactivated or attenuated pathogens, or components of a pathogen (nucleic acid, protein), that when administered stimulate a protective immune response. — Harrison's Principles of Internal Medicine 22E
2. Active Immunization
The host's own immune system is stimulated to produce antibodies and memory cells. Responses include:
- Primary response: Peak antibody titers achieved several weeks after initial administration; may require multiple doses, especially with inactivated vaccines
- Secondary (anamnestic) response: Triggered by booster doses — rapid antibody induction within days
- Both humoral (serum antibodies, mucosal IgA) and cellular (T-lymphocyte) responses are generated
Types of Vaccines
| Technology | Description | Examples | Advantages | Disadvantages |
|---|---|---|---|---|
| Live attenuated | Weakened forms of pathogen | MMR, varicella, OPV, oral rotavirus, nasal influenza | Mimics natural infection; durable immunity; usually 1–2 doses | Safety concerns in immunocompromised/pregnant; stability issues |
| Inactivated (killed) | Pathogen or toxin rendered non-living by heat or chemicals | IPV, hepatitis A, whole-cell pertussis, tetanus toxoid, diphtheria toxoid | Broad immune response; noninfectious | Multiple doses needed; may require adjuvant; more reactogenic |
| Purified protein/subunit | Specific antigenic proteins from pathogen | Influenza (split), acellular pertussis, recombinant shingles (RZV) | Low reactogenicity; noninfectious | May require adjuvant; limited cross-protective immunity |
| Polysaccharide–protein conjugates | Polysaccharide antigen conjugated to protein carrier | Pneumococcal (PCV), meningococcal (MCV4), Hib conjugate, Vi-conjugate typhoid | Effective in all ages including infants; T-cell–dependent response | Technically difficult; one conjugate per serotype |
| Virus-like particles (VLPs) | Proteins arranged to resemble virus structure | Hepatitis B, HPV | Noninfectious; broad immune response | Lower stability; technically difficult |
| Replicating viral vector | Replicating nonpathogenic virus delivers antigen nucleic acid | VSV-based Ebola vaccine | Broad immune response | Pre-existing immunity to vector may blunt response |
| Non-replicating viral vector | Replication-deficient virus carries antigen | Chimpanzee adenovirus-based COVID-19 vaccines | Scalable manufacturing | Pre-existing vector immunity |
| Nucleic acid (mRNA/DNA) | Lipid nanoparticles (LNP) deliver mRNA for in vivo antigen production | COVID-19 mRNA vaccines (Pfizer-BioNTech, Moderna) | Rapid development; effective | May need boosters; cold-chain requirements |
— Harrison's Principles of Internal Medicine 22E, Table 128-1
3. Passive Immunization
Preformed antibodies are transferred to the host; provides immediate but short-lived protection.
Sources of Passive Antibodies
| Source | Mechanism | Duration | Examples |
|---|---|---|---|
| Pooled human immunoglobulin (IG) | IgG from multiple donors | Weeks to months | Hepatitis A post-exposure, measles prophylaxis |
| Specific (hyperimmune) immunoglobulin | High-titer IgG against specific antigen | Weeks to months | HBIG (hepatitis B), TIG (tetanus), HRIG (rabies), VZIg (varicella) |
| Monoclonal antibodies | Engineered antibodies with extended half-life | Months | Nirsevimab (RSV in infants), anti-SARS-CoV-2 mAbs |
| Maternal immunization / transplacental IgG | Maternal antibodies cross placenta | Months in neonate | Tdap, RSV vaccine in pregnancy |
| Animal antisera | Antibodies raised in animals | Short; risk of serum sickness | Snake antivenom, diphtheria antitoxin (historical) |
Key comparison:
- Active immunity: delayed onset (weeks), long-lasting (years, memory cells)
- Passive immunity: immediate onset, short-lived (weeks to months, no memory)
4. Adjuvants
Adjuvants are substances added to vaccines to non-specifically enhance immune responses, especially necessary in inactivated or protein-based vaccines.
| Adjuvant | Examples | Mechanism | Licensed use |
|---|---|---|---|
| Alum (aluminum salts) | Al(OH)₃, AlPO₄ | Depot effect; enhances antibody production | DTaP, hepatitis vaccines; oldest adjuvant (90+ years) |
| Oil-in-water emulsions | MF59, AS03 (contain squalene) | Recruits innate immune cells; enhances antigen uptake | Certain influenza vaccines |
| TLR agonists | MPL (TLR4), CpG (TLR9) | Innate pattern recognition → enhanced adaptive response | AS04 (HPV), AS01B (RZV shingles) |
5. Herd (Community) Immunity
When a sufficient proportion of a population is immune, transmission is interrupted even in unimmunized individuals. The threshold varies by pathogen's reproductive number (R₀):
- Measles (R₀ ~12–18): ~92–95% coverage needed
- Polio (R₀ ~5–7): ~80–85% coverage needed
6. Special Considerations
Immunocompromised Patients
- Live attenuated vaccines are contraindicated in severely immunocompromised individuals (HIV with low CD4, chemotherapy, etc.)
- BCG (live M. bovis) is contraindicated in HIV-positive patients
- Inactivated vaccines are generally safe but may be less immunogenic
Toxoid Vaccines
- Bacterial exotoxins treated with formaldehyde → toxoid (antigenically intact, non-toxic)
- Examples: Tetanus toxoid, Diphtheria toxoid
- Tetanus: treated with passive TIG; prevented by active toxoid
Polysaccharide vs. Conjugate Vaccines
| Plain polysaccharide (e.g., PPSV23) | Conjugate (e.g., PCV13/PCV15/PCV20) | |
|---|---|---|
| Immune response | T-cell independent | T-cell dependent |
| Effective in infants | No | Yes |
| Memory | Minimal | Robust |
| Indicated in | Adults ≥65, high-risk adults | All children, certain adults |
7. BCG Vaccine (Mycobacterial Example)
- Live attenuated Mycobacterium bovis strain
- Widely used in TB-endemic countries
- Most effective when given early in life; less effective in adults
- Contraindicated in immunocompromised patients
- Causes positive tuberculin skin test (TST), but IFN-γ release assays (IGRAs) are not affected by BCG — preferred for screening BCG-vaccinated populations
- Not routinely used in low-incidence countries (US, Western Europe)
— Medical Microbiology 9e, Chapter on Mycobacterium
8. Vaccine Development Phases
| Phase | Purpose | Scale |
|---|---|---|
| Phase I | Safety, dosing, basic immunogenicity | Small (dozens); dose-escalation with DSMC oversight |
| Phase II | Expanded safety, immune responses in broader populations | Hundreds |
| Phase III | Efficacy (prevention of laboratory-confirmed disease); randomized, blinded, placebo-controlled | Thousands to hundreds of thousands |
| Lot-consistency | Ensures manufacturing reproducibility before licensure | |
| Post-licensure (Phase IV) | Long-term safety surveillance (pharmacovigilance) | Population-level |
Controlled Human Infection Models (CHIMs) can expedite development where phase 3 field trials are impractical (e.g., oral cholera vaccine, typhoid, influenza).
Summary
| Feature | Active Immunization | Passive Immunization |
|---|---|---|
| Mechanism | Host generates own antibodies | Preformed antibodies transferred |
| Onset | Delayed (2–4 weeks) | Immediate |
| Duration | Long-lasting (years) | Short (weeks–months) |
| Memory | Yes | No |
| Use | Prevention (pre-exposure) | Treatment or short-term prevention (post-exposure) |
| Examples | MMR, DTP, influenza, COVID-19 vaccines | HBIG, HRIG, TIG, IVIG, monoclonal antibodies |
Sources: Harrison's Principles of Internal Medicine 22E (2025); Medical Microbiology 9e
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