Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017

Abstract

Background: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly.

Methods: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013-2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients.

Results: Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45-59) for IIV4 versus 45% (95% CI, 34-54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency.

Conclusions: The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

Keywords: effectiveness; inactivated influenza vaccine; influenza B lineage; quadrivalent; trivalent.

Figure 1.

Influenza vaccine distribution and B lineage virus circulation in the US Influenza Vaccine Effectiveness (Flu VE) Network. A, Distribution of IIV3 and IIV4 during the 2011–2012 to 2016–17 seasons. B, Influenza B lineage circulation in the US Flu VE network during the 2011–2012 to 2016–2017 seasons. Abbreviations: IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine.

Figure 2.

Adjusted VE estimates of trivalent and quadrivalent formulations against any influenza B and each B lineage in the US Influenza Vaccine Effectiveness Network. A, Adjusted VE % against influenza B and each B lineage, including the B lineage virus included in IIV3 during 6 seasons from 2011–2012 to 2016–2017. B, Adjusted VE % against any influenza B and each B lineage, including the B lineage virus included in IIV3 and IIV4 during 4 seasons when both IIV3 and IIV4 were used (2013–2014 to 2016–2017). A priori, VE estimates were simple adjusted for age, season, study site, calendar week (pre-peak and peak influenza activity and post-peak tertiles, per site per season), and the presence of any high-risk, chronic medical condition. Abbreviations: CI, confidence interval; IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine; VE, vaccine effectiveness.

Figure 3.

Adjusted rOR of IIV3 versus IIV4 (reference) during 4 seasons from 2013–2014 to 2016–2017 of any influenza B; of each B lineage virus infection, including B/Yamagata– or B/Victoria–containing IIV3 seasons; and of the B lineage virus included in IIV3 versus lineage-mismatched IIV3. A priori, rOR estimates were simple adjusted for age, season, site, calendar week (pre-peak and peak influenza activity and post-peak tertiles, per site per season) and the presence of any high-risk, chronic medical condition. Data were not reported when the number of vaccinated cases was <5. Abbreviations: CI, confidence interval; IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine; rOR, relative odds ratios.