Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States

Abstract

Background: The predominant strain during the 2013-2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009.

Methods: The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2-17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed.

Results: We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR-confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%-61%). Among fully vaccinated children aged 2-17 years, the effectiveness of LAIV4 was 17% (95% CI, -39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%-74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season.

Conclusions: During 2013-2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States.

Keywords: influenza; influenza vaccine; influenza vaccine effectiveness; vaccine effectiveness.

Figure 1.

Algorithm for determination of 2013–2014 influenza vaccination status and inclusion/exclusion in the analytic data set. ^aExclusions denote 38 test-negative control subjects enrolled outside of the influenza A and B virus infection outbreak period, 133 partially vaccinated children, and 13 enrolled subjects with inconclusive or unrepeatable polymerase chain reaction results. Abbreviations: EIR, electronic immunization record (defined as electronic medical record, employee health record, and state immunization registry); MI, Michigan; PA, Pennsylvania; TX, Texas; WA, Washington; WI, Wisconsin.

Figure 2.

Vaccine effectiveness (VE) against 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09)–related medically attended acute respiratory illness (MAARI) during the 2013–2014 influenza season among children aged 2–8 years, by receipt or no receipt of ≥1 dose of current inactivated influenza vaccine (IIV) or live attenuated influenza vaccine (LAIV) and receipt or no receipt of any prior A(H1N1)pdm09-containing vaccine since the 2009 influenza pandemic. Trivalent IIV (IIV3) and quadrivalent IIV (IIV4) were both available only in 2013–2014, IIV3 was the only IIV available during the prior 4 seasons, and monovalent A(H1N1)pdm09-containing IIV was available in 2009–2010. Quadrivalent LAIV was the only LAIV available during 2013–2014, trivalent LAIV was available during the prior 4 seasons, and monovalent A(H1N1)pdm09-containing LAIV was available in 2009–2010. For children aged 2–8 years, we included those fully or partially vaccinated against A(H1N1)pdm09, per the definition of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) [6]. Children who received 2 doses of the same vaccine type during the current season or 1 dose of either vaccine type during the current season with ≥1 dose/s of any a(H1N1)pdm09-containing vaccine since 2009 were considered fully vaccinated. Children who received both IIV and LAIV in 2013–2014 were excluded. VE was estimated as 100 × [1− odds ratio], where the odds ratio was calculated as the ratio of the odds of being vaccinated among subjects with MAARI who were positive for influenza virus by polymerase chain reaction (PCR; ie, cases) to the odds of being vaccinated among subjects with MAARI who were negative for influenza virus by PCR. Odds ratios were estimated using logistic regression. The comparison VE model adjusted for site, age, calendar time, any high-risk condition, sex, race/ethnicity, general health status, and interval from illness onset to enrollment. VEs for those with a VE or a lower bound of the 95% confidence interval (CI) of less than −25% were as follows: full in 2013–2014 (current LAIV), 21% (95% CI, −92% to 68%); partial in 2013–2014 (current IIV), 34% (95% CI, −285% to 89%); partial by 2012–2013 (no current), 30% (95% CI, −74% to 72%). ^aIncludes children partially vaccinated in the current season with IIV3/ or IIV4 alone, as there was no partially vaccinated child with LAIV4 administered during the current season.

Figure 3.

Vaccine effectiveness (VE) against 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09)–related medically attended acute respiratory illness (MAARI) for the 2013–2014 season among persons aged ≥9 years, by receipt or no receipt of current inactivated influenza vaccine (IIV; defined as trivalent IIV, quadrivalent IIV, or unknown influenza vaccine) and receipt or no receipt of any prior A(H1N1)pdm09-containing vaccine dose since the 2009 influenza pandemic. Children who received both IIV and live attenuated influenza vaccine in 2013–2014 were excluded. VE was estimated as 100 × [1− odds ratio], where the odds ratio was calculated as the ratio of the odds of being vaccinated among subjects with MAARI who were positive for influenza virus by polymerase chain reaction (PCR; ie, cases) to the odds of being vaccinated among subjects with MAARI who were negative for influenza virus by PCR. Odds ratios were estimated using logistic regression. The full VE model was adjusted for site, age, calendar time, any high-risk condition, sex, race/ethnicity, general health status, and interval from illness onset to enrollment. VE was not reported (NR) if the lower bound of the 95% confidence interval (CI) was less than −99%. VEs for those with a VE or lower bound of the 95% CI of less than −25% were as follows: ages 9–17 years (current dose only), 70% (95% CI, −169% to 97%).