Classification of vaccines
A vaccine is a biological preparation that exposes the immune system to an antigen or to genetic instructions for producing an antigen. It induces active, specific immunity and immunological memory without causing the usual clinical disease.
Vaccines can be classified in several complementary ways:
- By nature of the immunizing material
- By whether the organism is live or non-living
- By technological platform
- By route and composition
- By number of antigens or diseases covered
The most important practical classification is by the type of antigen/platform.
1. Live attenuated vaccines
These contain live organisms that have been weakened, or attenuated, so that they replicate to a limited extent but normally do not cause disease in immunocompetent recipients.
Mechanism
Because they resemble natural infection, they stimulate:
- Humoral immunity, including neutralizing antibodies
- Cell-mediated immunity
- Often mucosal immunity when administered orally or intranasally
- Long-lasting immune memory
Features
- Usually highly immunogenic
- Often need fewer doses than non-live vaccines
- Usually do not require an adjuvant
- Must be stored carefully because viability is necessary
- May very rarely cause disease in severely immunocompromised persons
- Generally avoided in pregnancy and significant immunodeficiency
Examples
Live viral vaccines
- BCG is bacterial, not viral, but is commonly remembered with live vaccines
- Measles
- Mumps
- Rubella
- MMR and MMRV
- Varicella
- Live zoster vaccine
- Rotavirus vaccine
- Oral poliovirus vaccine, OPV
- Yellow fever vaccine
- Live attenuated influenza vaccine, intranasal
- Smallpox vaccine
Live bacterial vaccines
- BCG vaccine
- Oral typhoid vaccine, Ty21a
- Oral live cholera vaccines in certain settings
Goodman and Gilman lists BCG, oral typhoid and oral cholera among live bacterial vaccines, and MMR, varicella, rotavirus, intranasal influenza and yellow fever among live viral vaccines. Goodman & Gilman's The Pharmacological Basis of Therapeutics, vaccine section.
Limitations
- Interference by maternal antibodies can reduce response in infants.
- Storage and cold-chain failure can reduce potency.
- OPV carries a rare risk of vaccine-associated paralytic poliomyelitis and vaccine-derived poliovirus transmission, which is why many countries use IPV in routine programs.
- Not routinely given to people with severe cellular immunodeficiency or to pregnant individuals.
2. Inactivated or killed whole-organism vaccines
These contain whole bacteria or viruses that have been killed by heat, chemicals, or radiation. They cannot replicate in the recipient.
Mechanism and features
- Primarily stimulate antibody-mediated immunity.
- Cannot revert to virulence or cause infection.
- Safer for immunocompromised people than live vaccines in most circumstances.
- Usually require multiple primary doses and booster doses.
- Often require an adjuvant.
Examples
Inactivated viral vaccines
- Inactivated poliovirus vaccine, IPV
- Hepatitis A vaccine
- Rabies vaccine
- Most injectable influenza vaccines
- Japanese encephalitis vaccine
- Tick-borne encephalitis vaccine
- Some COVID-19 vaccines, for example whole-virion inactivated products
Inactivated bacterial vaccines
- Whole-cell pertussis vaccine
- Killed cholera vaccine
- Killed typhoid vaccine
- Plague vaccine, where used
Advantages
- No risk of replication or vaccine-acquired infection
- Relatively stable compared with live vaccines
- Can be given when live vaccines are contraindicated
Disadvantages
- Immune response is generally less durable than after live vaccination.
- Multiple doses and boosters are commonly needed.
- They usually generate little mucosal immunity.
3. Toxoid vaccines
Some bacteria cause disease mainly through an exotoxin rather than by invasive multiplication alone. A toxoid vaccine contains an inactivated bacterial toxin that retains its antigenicity but has lost toxicity.
Mechanism
The vaccine induces antitoxin antibodies, which neutralize the toxin when the vaccinated person encounters the organism.
Examples
- Tetanus toxoid
- Diphtheria toxoid
These are used alone or in combination vaccines:
- DTaP: diphtheria, tetanus and acellular pertussis
- DT
- Td
- Tdap
Features
- Safe and non-replicating
- Need primary series plus periodic booster doses because antibody concentrations decline
- Protection is chiefly against toxin-mediated disease, not always against colonization or carriage
4. Subunit vaccines
Subunit vaccines contain only selected antigenic components of a pathogen rather than the complete organism. The antigen may be a protein, glycoprotein, purified surface component, or another defined antigenic fragment.
Features
- Cannot cause the infection
- Usually have fewer adverse effects than whole-cell vaccines
- Often require adjuvants and booster doses
- Antigen selection is important because only included antigens induce protection
Examples
- Acellular pertussis vaccine
- Recombinant hepatitis B vaccine
- Recombinant zoster vaccine
- Human papillomavirus, HPV, vaccine
- Some influenza vaccines, including split-virus or purified subunit formulations
- Protein-based COVID-19 vaccines
The Harriet Lane Handbook describes subunit, recombinant, polysaccharide and conjugate vaccines as using defined pathogen components such as protein, sugar, or capsid, with boosters sometimes required. The Harriet Lane Handbook, Active Immunization section.
Subtypes of subunit vaccines
A. Protein subunit vaccines
Contain purified pathogen proteins.
Examples:
- Acellular pertussis
- Recombinant zoster vaccine
- Recombinant hepatitis B vaccine
B. Virus-like particle vaccines
These contain self-assembled viral structural proteins that resemble a virus but contain no viral genetic material. They cannot replicate.
Examples:
- HPV vaccine
- Some hepatitis B vaccine formulations
C. Recombinant vaccines
The antigen is produced using recombinant DNA technology, often in yeast, bacteria, insect cells, or mammalian cells.
Examples:
- Hepatitis B vaccine, containing recombinant hepatitis B surface antigen
- HPV vaccine
- Recombinant zoster vaccine
5. Polysaccharide vaccines
These contain purified capsular polysaccharides from bacteria.
Mechanism
They primarily induce a T-cell-independent B-cell response.
Consequences of T-cell-independent response
- Mainly IgM, with limited class switching
- Weak immunologic memory
- Less effective in children younger than 2 years
- Repeated doses may produce hyporesponsiveness for some antigens
- Limited effect on nasopharyngeal carriage
Examples
- Pneumococcal polysaccharide vaccine, PPSV23
- Meningococcal polysaccharide vaccine
- Typhoid Vi polysaccharide vaccine
Goodman and Gilman lists meningococcal polysaccharide vaccine, polyvalent pneumococcal vaccine and typhoid Vi polysaccharide vaccine under bacterial polysaccharide vaccines. Goodman & Gilman's The Pharmacological Basis of Therapeutics, vaccine section.
6. Conjugate vaccines
A conjugate vaccine contains a bacterial capsular polysaccharide chemically linked to a carrier protein, such as tetanus toxoid, diphtheria toxoid, or CRM197 diphtheria protein.
Why conjugation is important
Polysaccharide alone causes a poor T-cell-independent response in infants. Linking it to protein converts the response into a T-cell-dependent immune response.
This leads to:
- Better response in infants and young children
- Immunologic memory
- Antibody class switching, especially IgG
- Strong booster response
- Reduced nasopharyngeal carriage and herd protection
Examples
- Hib conjugate vaccine
- Pneumococcal conjugate vaccines, such as PCV
- Meningococcal conjugate vaccines, such as MenACWY
- Typhoid conjugate vaccine
The distinction matters clinically: compared with plain polysaccharide vaccines, conjugate vaccines induce memory and improve protection in young children.
7. Nucleic acid vaccines
These do not supply the antigen itself. Instead, they provide genetic instructions that allow host cells to produce the antigen, which is then recognized by the immune system.
A. mRNA vaccines
These contain messenger RNA, usually packaged in lipid nanoparticles. Host-cell ribosomes translate the mRNA into antigenic protein.
Features
- No live pathogen
- No integration into human DNA
- Capable of inducing antibody and T-cell responses
- Rapid platform design after an antigen sequence is known
Examples
- Several COVID-19 mRNA vaccines
B. DNA vaccines
These contain plasmid DNA encoding an antigen.
Features
- Stable platform, often easier to store than mRNA
- May require special delivery systems, such as electroporation
- Used widely in veterinary medicine and under continuing development for many human indications
8. Viral-vector vaccines
These use a modified virus as a delivery system for genetic material encoding an antigen of another pathogen.
The vector enters cells, which then produce the target antigen.
Types
- Non-replicating viral vectors: vector enters cells but cannot complete replication.
- Replicating viral vectors: vector replicates to some degree and may produce stronger immune stimulation.
Examples
- Adenoviral-vector COVID-19 vaccines
- Ebola vaccine using vesicular stomatitis virus vector
- Some experimental malaria, tuberculosis and HIV vaccines
Advantages
- Induce both antibody and cellular immune responses
- Can be manufactured using established vector platforms
Limitations
- Pre-existing immunity to the vector can lower effectiveness.
- Subsequent doses using the same vector may be less immunogenic.
- Safety and reactogenicity vary by vector platform.
The WHO groups viral-vector and nucleic-acid platforms among newer vaccine technologies, alongside traditional live-attenuated, inactivated, polysaccharide and toxoid vaccines and modern conjugate and protein-based vaccines in its
global vaccine market report.
9. Combination vaccines
A combination vaccine protects against more than one disease in one injection or formulation.
Examples
- DTaP
- DTaP-IPV
- DTaP-HepB-IPV
- DTaP-IPV-Hib
- MMR
- MMRV
- Hepatitis A and hepatitis B combination vaccine
- Pentavalent vaccine: DPT, hepatitis B and Hib
- Hexavalent vaccine: DTaP, IPV, Hib and hepatitis B
Advantages
- Fewer injections
- Better adherence to immunization schedules
- Fewer clinic visits
- Simplified logistics and record-keeping
A combination vaccine is not necessarily a separate antigen technology. For example, it can combine toxoids, inactivated antigens, protein subunits and conjugate components.
10. Classification by valency
Valency denotes the number of strains, serotypes, or antigenic types included.
-
Monovalent: one antigenic type
Example: monovalent hepatitis B vaccine.
-
Bivalent: two types or strains
Example: bivalent oral poliovirus vaccine.
-
Trivalent: three types or strains
Example: trivalent influenza vaccine.
-
Quadrivalent: four types or strains
Example: quadrivalent influenza vaccine or quadrivalent meningococcal vaccine.
-
Multivalent or polyvalent: several antigenic types
Example: PPSV23, which targets multiple pneumococcal serotypes; multivalent HPV vaccines.
Valency should not be confused with the number of diseases prevented by a combination vaccine.
11. Classification by route of administration
Oral vaccines
- OPV
- Rotavirus vaccine
- Oral typhoid vaccine
- Some oral cholera vaccines
They can stimulate intestinal mucosal immunity.
Intranasal vaccines
- Live attenuated influenza vaccine
Intradermal vaccines
- BCG
- Some rabies vaccine schedules
Subcutaneous vaccines
- MMR
- Varicella
- Yellow fever
Intramuscular vaccines
- DTaP/Tdap
- Hepatitis A and B
- IPV
- HPV
- Influenza vaccines
- Pneumococcal and meningococcal vaccines
- Most COVID-19 vaccines
12. Classification by effect on the immune system
Active immunization
Administration of antigen or genetic antigen instructions to stimulate the recipient's own immune response.
Examples:
- All routine vaccines
- Toxoids
- Live, killed, subunit, conjugate, vector and mRNA vaccines
Features:
- Protection develops after days to weeks
- Generates memory
- Generally long-lasting, though boosters may be necessary
Passive immunization
Administration of preformed antibodies. This is not vaccination in the strict sense.
Examples:
- Rabies immunoglobulin
- Tetanus immunoglobulin
- Hepatitis B immunoglobulin
- Antivenom
- Maternal antibodies transferred across the placenta
- Some monoclonal antibodies, for example preventive antibodies against RSV
Features:
- Immediate but temporary protection
- No immunological memory
Summary table
| Vaccine type | Main material | Typical immune response | Examples | Main limitation |
|---|
| Live attenuated | Weakened live organism | Strong humoral and cellular immunity | BCG, MMR, varicella, OPV, rotavirus | Avoid in severe immunodeficiency and pregnancy |
| Inactivated | Killed whole organism | Mainly antibody response | IPV, rabies, hepatitis A, injectable influenza | Multiple doses and boosters |
| Toxoid | Inactivated toxin | Antitoxin antibody | Tetanus, diphtheria | Periodic boosters needed |
| Protein/subunit | Selected antigenic protein | Mainly antibody, sometimes T-cell response | Hepatitis B, acellular pertussis, zoster | Often needs adjuvant and boosters |
| Virus-like particle | Noninfectious protein shell | Strong neutralizing antibody response | HPV | Limited to included antigen types |
| Polysaccharide | Bacterial capsule antigen | T-cell-independent antibody response | PPSV23, typhoid Vi | Weak in children under 2 years, little memory |
| Conjugate | Polysaccharide linked to protein | T-cell-dependent response with memory | Hib, PCV, MenACWY, typhoid conjugate | More complex and costly production |
| Viral vector | Vector virus carrying antigen gene | Antibody plus T-cell response | Ebola and some COVID-19 vaccines | Anti-vector immunity may affect response |
| mRNA/DNA | Genetic instructions for antigen | Antibody and T-cell response | mRNA COVID-19 vaccines | Storage and delivery constraints vary |
| Combination | More than one antigen/product | Depends on components | DTaP-IPV-Hib, MMR, pentavalent | Compatibility and schedule complexity |
Key distinction to remember:
- Live vaccines replicate minimally and usually give strong, durable immunity.
- Inactivated, toxoid and subunit vaccines cannot replicate and commonly need repeated doses or boosters.
- Plain polysaccharide vaccines have poor memory responses in young children.
- Conjugate vaccines overcome this limitation by attaching polysaccharide to a protein carrier.