Since 2013, quadrivalent influenza vaccines containing two B viruses gradually replaced trivalent vaccines in the United States. We compared vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3) against illness due to influenza B during the transition when IIV4 use increased rapidly.
The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25,019 of 42,600 outpatients aged ≥6 months enrolled within 7 days of illness-onset during six seasons from 2011-2012. Upper respiratory specimens were tested for influenza virus type and B-lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of influenza B infection overall, and by B lineage among vaccinated versus unvaccinated participants. Over four seasons from 2013-2014, we compared relative odds of influenza B infection among IIV4 versus IIV3 recipients.
Trivalent vaccines included the predominantly circulating B lineage in four of six seasons. During four influenza seasons when both IIV4 and IIV3 were widely used, overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45 to 59) for IIV4 versus 45% (95% CI, 34 to 54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illness related to any influenza B favored neither vaccine valency.
Uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.