Quadrivalent (Tetra) Influenza Vaccine Recommendation
Either quadrivalent or trivalent influenza vaccines are acceptable options, as ACIP expresses no preference between them for any age group. 1
Key Guideline Position
The Advisory Committee on Immunization Practices (ACIP) has consistently stated across multiple seasons (2017-2022) that no preference is expressed for either quadrivalent or trivalent vaccines, despite quadrivalent vaccines being designed to provide broader protection against circulating influenza B virus strains by including both B lineages (Victoria and Yamagata) rather than just one. 1
Understanding the Difference
Quadrivalent vaccines (IIV4) contain four viral strains: two influenza A strains plus one virus from each of the two influenza B lineages (Victoria and Yamagata). 1
Trivalent vaccines (IIV3) contain three viral strains: two influenza A strains plus one influenza B virus from a single lineage. 1
The theoretical advantage of quadrivalent vaccines is broader protection against influenza B viruses, which can reduce the impact of B lineage mismatches that occur when the circulating B lineage differs from the one included in trivalent vaccines. 1
Real-World Effectiveness Evidence
The clinical benefit of quadrivalent over trivalent vaccines is modest and inconsistent:
A large U.S. study (2011-2017) found overall effectiveness against any influenza B was 53% for IIV4 versus 45% for IIV3—a difference that did not strongly favor either vaccine valency for protection against any influenza B illness. 2
An Israeli cohort study during high influenza B activity seasons showed QIV recipients had lower odds of hospitalization (OR 0.89-0.92) and emergency department visits (OR 0.84-0.91) compared to TIV recipients. 3
However, the uptake of quadrivalent vaccines has not been associated with substantially increased population-level protection against influenza B illness overall, despite higher effectiveness against the added B lineage specifically. 2
Practical Considerations
In clinical practice, receive whichever age-appropriate influenza vaccine is readily available:
Both formulations provide protection against the most important influenza strains (the two influenza A subtypes). 1
The primary goal is achieving vaccination coverage; delaying or missing vaccination while seeking a specific formulation is counterproductive. 1
For adults 18-64 years who are not pregnant or immunocompromised, either standard-dose trivalent or quadrivalent (cell-based, egg-based, MF59-adjuvanted, or recombinant) influenza vaccine is appropriate for the 2025-2026 season. 4
For adults ≥65 years who are not immunocompromised, either high-dose trivalent or high-dose quadrivalent egg-based influenza vaccine is recommended. 4
Cost-Effectiveness Context
While quadrivalent vaccines typically cost 15-50% more than trivalent vaccines, cost-effectiveness analyses generally support their use when vaccination coverage remains equal between the two options. 5, 6 However, in resource-limited settings where higher vaccine prices reduce overall coverage, achieving broader population coverage with trivalent vaccines may yield better public health outcomes than lower coverage with quadrivalent vaccines. 5
Common Pitfalls to Avoid
Do not delay vaccination waiting for a specific vaccine formulation—timing of vaccination is more critical than vaccine valency. 1
Do not assume quadrivalent vaccines provide dramatically superior protection—the ACIP's lack of preference reflects the modest real-world differences in effectiveness. 1, 2
Do not confuse vaccine valency with other important vaccine characteristics such as high-dose or adjuvanted formulations for older adults, which have clearer preferential recommendations. 4