Quadrivalent vs. Trivalent Flu Vaccines
Quadrivalent flu vaccines offer broader protection against influenza B viruses compared to trivalent vaccines by including strains from both B lineages (Victoria and Yamagata), while trivalent vaccines contain only one B lineage strain.
Key Differences Between Quadrivalent and Trivalent Flu Vaccines
Composition
Trivalent vaccines (IIV3): Contain three influenza virus strains:
- Two influenza A strains (typically H1N1 and H3N2)
- One influenza B strain (from either Victoria or Yamagata lineage) 1
Quadrivalent vaccines (IIV4): Contain four influenza virus strains:
- Two influenza A strains (same as trivalent)
- Two influenza B strains (one from each lineage: Victoria and Yamagata) 1
Protective Coverage
Quadrivalent vaccines were developed to address a significant clinical problem: since the 1980s, two antigenically distinct lineages of influenza B viruses have circulated globally. Vaccination against one B lineage confers little cross-protection against the other lineage 1.
The inclusion of both B lineages in quadrivalent vaccines provides broader protection, especially important because:
- It has proven difficult to predict which B lineage will predominate in a given season 1
- Approximately 31% of B strain disease was not covered by the trivalent vaccine over a 10-year period 2
Antigen Content
- Standard-dose trivalent vaccines contain 15 μg of hemagglutinin (HA) from each strain (45 μg total) 1
- Standard-dose quadrivalent vaccines contain 15 μg of hemagglutinin from each strain (60 μg total) 1
- High-dose trivalent vaccine (Fluzone High-Dose) contains 60 μg of HA per strain (180 μg total) 1
Clinical Implications
Efficacy and Immunogenicity
- Quadrivalent vaccines demonstrate immunogenicity comparable to trivalent vaccines for the shared strains 3, 4
- Quadrivalent vaccines show superior immune response against the additional B strain not contained in trivalent vaccines 3
- Both vaccine types meet European (CHMP) and US (CBER) licensing criteria for the strains they contain 3
Official Recommendations
The Advisory Committee on Immunization Practices (ACIP) states:
- No preference is expressed for either quadrivalent or trivalent vaccines 1
- A licensed, age-appropriate influenza vaccine product should be used 1
- Vaccination should not be delayed to obtain a specific product when an appropriate one is already available 1
Practical Considerations
Availability
For recent influenza seasons, most standard-dose, unadjuvanted inactivated influenza vaccines have been quadrivalent formulations 1. However, some specialized vaccines remain trivalent:
- High-dose unadjuvanted vaccine (HD-IIV3, Fluzone High-Dose)
- Adjuvanted vaccine (aIIV3, Fluad)
Cost-Effectiveness
Quadrivalent influenza vaccines are expected to offer substantial cost-effectiveness benefits in seasons where the B lineage selected for inclusion in trivalent vaccines does not match the dominant circulating strain 4.
Special Populations
Children
Both trivalent and quadrivalent formulations are available for children, with specific dosing considerations:
- For children 6-35 months, multiple quadrivalent products are licensed with different approved dose volumes 1
- Children aged 36 months through 17 years should receive 0.5 mL per dose 1
Older Adults
High-dose trivalent vaccine (Fluzone High-Dose) is specifically licensed for persons aged ≥65 years 1.
Common Pitfalls to Avoid
Assuming all flu vaccines are the same: Different formulations exist for different age groups and populations.
Delaying vaccination to get a specific formulation: The ACIP recommends not delaying vaccination to obtain a specific product when an appropriate one is already available 1.
Incorrect dosing in young children: Care must be taken to administer the appropriate dose volume for each specific product in children aged 6-35 months 1.
Misunderstanding contraindications: History of severe allergic reaction to the vaccine or any of its components is a contraindication for both vaccine types 1.
In summary, while quadrivalent vaccines offer broader protection against circulating influenza B viruses by including both lineages, both trivalent and quadrivalent vaccines are considered effective options for influenza prevention. The choice between them should be based on availability, age appropriateness, and specific patient factors.