Vaccine combinations

Vaccine combinations are pharmaceutical formulations that contain two or more antigens from different pathogens or pathogen strains, designed to confer immunity against multiple infectious diseases with a single injection or administration schedule. Combination vaccines are an essential component of modern immunization programs globally, especially in pediatric vaccination schedules, as they help reduce the number of injections, improve patient adherence, minimize healthcare visits, and optimize logistics related to vaccine storage and administration.

These formulations can be classified based on their antigenic composition (e.g., bacterial, viral, toxoid) and the number of diseases they protect against (e.g., bivalent, trivalent, quadrivalent, or hexavalent vaccines). They are available in monodose prefilled syringes, multidose vials, or reconstitution kits, depending on the manufacturer and use case.

---

Types of Vaccine Combinations

Combination vaccines may be classified into the following categories:

1. Bacterial Combinations

   • Examples: DTaP (Diphtheria, Tetanus, Pertussis), Td, DT, Pentavalent vaccines (DTwP-HepB-Hib)

2. Viral Combinations

   • Examples: MMR (Measles, Mumps, Rubella), MMRV (includes Varicella), Twinrix (Hepatitis A + B), Influenza quadrivalent

3. Bacterial-Viral Combinations

   • Examples: Hexavalent vaccines (DTaP-IPV-HepB-Hib)

4. Multivalent Single-Pathogen Vaccines

   • Examples: HPV vaccines (bivalent, quadrivalent, 9-valent), Influenza (trivalent/quadrivalent), Pneumococcal conjugate vaccines (e.g., PCV13, PCV20), Rotavirus vaccines (monovalent or pentavalent)

---

Benefits of Combination Vaccines

• Improved patient compliance through fewer injections

• Decreased distress in children and caregivers

• Simplified vaccination schedules

• Reduced healthcare visits and resource use

• Cost-effectiveness from shared components (e.g., adjuvants, preservatives)

• Higher immunization coverage rates

---

Commonly Used Combination Vaccines (Generic Components and Brand Names)

Combination	Generic Composition	Common Brands
DTaP	Diphtheria toxoid + Tetanus toxoid + Acellular pertussis	Daptacel®, Infanrix®
Tdap	Tetanus toxoid + Reduced diphtheria toxoid + Acellular pertussis	Boostrix®, Adacel®
DTwP-HepB-Hib	Diphtheria + Tetanus + Whole-cell pertussis + Hepatitis B + Haemophilus influenzae type b	Pentavac®, Shan5®, Quinvaxem®
DTaP-IPV-Hib	Diphtheria + Tetanus + Acellular pertussis + Inactivated Polio + Haemophilus influenzae type b	Pentacel®
DTaP-IPV-HepB-Hib (Hexavalent)	Diphtheria + Tetanus + Acellular pertussis + Polio + Hepatitis B + Haemophilus influenzae b	Hexaxim®, Infanrix Hexa®, Vaxelis®
MMR	Live attenuated Measles + Mumps + Rubella viruses	M-M-R II®, Priorix®
MMRV	Live attenuated Measles + Mumps + Rubella + Varicella	ProQuad®
Twinrix	Inactivated Hepatitis A + Recombinant Hepatitis B	Twinrix®
Pediarix	DTaP + Hepatitis B + IPV	Pediarix®
Kinrix	DTaP + IPV	Kinrix®
Quadracel	DTaP + IPV	Quadracel®
Influenza (Quadrivalent)	2 A strains (e.g., H1N1, H3N2) + 2 B strains	Fluarix Quadrivalent®, Fluzone Quadrivalent®
HPV (9-valent)	HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58	Gardasil 9®
Pneumococcal (PCV13/PCV20)	13 or 20 pneumococcal serotypes conjugated to diphtheria CRM197 protein	Prevnar 13®, Prevnar 20®
Rotavirus	5 strains (human-bovine reassortants) or single human strain (monovalent)	RotaTeq® (pentavalent), Rotarix® (monovalent)
Comvax (discontinued)	Hib + Hepatitis B	Formerly used in U.S.

Selected Examples and Detailed Generic Information

1. Hexavalent Vaccine (DTaP-IPV-HepB-Hib)

• Generics: Diphtheria toxoid, Tetanus toxoid, Acellular pertussis antigens (e.g., PT, FHA), Inactivated polio (types 1-3), Recombinant Hepatitis B surface antigen (rHBsAg), Hib polysaccharide conjugated to tetanus protein

• Brands: Hexaxim®, Infanrix Hexa®, Vaxelis®

• Doses: 3 primary doses (2, 4, 6 months) + booster

• Route: Intramuscular

• Use: Pediatric primary immunization

---

2. MMR and MMRV Vaccines

• Generics:

  • MMR: Live attenuated measles (Edmonston strain), mumps (Jeryl Lynn or RIT4385), and rubella (Wistar RA 27/3)

  • MMRV: MMR + varicella (live attenuated Oka strain)

• Brands: M-M-R II®, Priorix®, ProQuad®

• Use: Routine pediatric immunization at 12–15 months and 4–6 years

• Caution: MMRV has a slightly higher risk of febrile seizures in <2 years

---

3. Twinrix (Hepatitis A + B)

• Generics: Inactivated Hepatitis A virus (HAV) + Recombinant Hepatitis B surface antigen (HBsAg)

• Use: Adults and children aged ≥1 year at risk for both HAV and HBV

• Schedule: 3 doses (0, 1, 6 months) or accelerated 4-dose schedule (0, 7, 21 days + 12 months)

• Brand: Twinrix®

---

4. HPV Vaccines (Bivalent, Quadrivalent, 9-valent)

• Generics:

  • Bivalent: HPV 16, 18 (Cervarix®)

  • Quadrivalent: HPV 6, 11, 16, 18 (Gardasil®)

  • 9-valent: HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 (Gardasil 9®)

• Schedule: 2 or 3 doses depending on age

• Use: Prevention of cervical, anal, vulvar, penile, and oropharyngeal cancers

---

5. DTaP-IPV Combinations

• Generics: Diphtheria, Tetanus, Acellular pertussis (PT, FHA, PRN), Inactivated poliovirus (types 1-3)

• Brands: Kinrix®, Quadracel®

• Use: Booster at 4–6 years of age

---

6. Pentavalent Vaccine (DTwP-HepB-Hib)

• Generics: Whole-cell pertussis vaccine (DTwP), recombinant hepatitis B, conjugated Hib vaccine

• Brands: Pentavac®, Shan5®

• Use: Used primarily in WHO-EPI programs in LMICs

---

Pediatric Immunization Example Schedule (Combination Vaccines)

Age	Recommended Combination Vaccine
Birth	Hepatitis B (monovalent or part of combo)
2 mo	DTaP-IPV-HepB-Hib (Hexavalent), PCV13, Rotavirus
4 mo	DTaP-IPV-HepB-Hib, Rotavirus, PCV13
6 mo	DTaP-IPV-HepB-Hib (final dose), Influenza
12 mo	MMR or MMRV, PCV13 (booster), Hib (booster)
15 mo	Varicella (if not MMRV), HepA
4-6 yr	DTaP-IPV, MMRV

Contraindications

• Hypersensitivity to any component or previous dose

• Severe allergic reaction (e.g., anaphylaxis) to neomycin, gelatin, or yeast (component-dependent)

• Encephalopathy within 7 days of DTaP-containing vaccine

• Immunocompromised patients (for live vaccines like MMR, MMRV, varicella)

• Moderate or severe acute illness (vaccination deferred)

---

Warnings and Precautions

• MMRV: Febrile seizure risk in younger children—consider MMR + Varicella separately

• HPV: Syncope risk post-injection—observe for 15 minutes

• Combination vaccines may have increased local reactions due to antigenic load

• Storage: Cold chain required (typically 2–8°C); freezing damages most vaccines

• Timing: Follow national immunization guidelines strictly

---

Adverse Effects

Type	Examples
Local	Injection site pain, redness, swelling
Systemic	Fever, irritability, fatigue, headache, myalgia
Serious	Anaphylaxis (rare), febrile seizures (MMRV), Guillain-Barré syndrome (rare)

Drug Interactions

• Live vaccines: May need spacing with immunoglobulin therapy (e.g., MMR and IVIG)

• Immunosuppressants: Reduce efficacy of live vaccines

• Corticosteroids: High-dose therapy delays certain vaccinations

• Tuberculin test (PPD): May give false negatives after MMR/MMRV—space testing by ≥4 weeks

---

Advantages of Combination Vaccines in Public Health

• Enhanced herd immunity via improved vaccine uptake

• Reduced cold chain burden (fewer vials/doses to manage)

• Streamlined mass immunization campaigns

• Ideal for expanded programs on immunization (EPI) and national schedules