TY - JOUR
T1 - Randomized pragmatic trial of the comparative effectiveness of chicken egg-based inactivated, mammalian cell-culture-based inactivated, and recombinant protein quadrivalent seasonal influenza vaccines in United States Military Health System beneficiaries
AU - PAIVED Study Group
AU - Colombo, Rhonda E
AU - Richard, Stephanie A
AU - Schmidt, Kat
AU - Schofield, Christina
AU - Ganesan, Anuradha
AU - Campbell, Wesley
AU - Hrncir, David
AU - Lalani, Tahaniyat
AU - Mende, Katrin
AU - Markelz, Ana E
AU - Berjohn, Catherine M
AU - Housel, Laurie
AU - Becher, Dorothy
AU - Zell, Elizabeth R
AU - Ewing, Dan
AU - Sundaram, Appavu K
AU - Modi, Jitendrakumar R
AU - Saperstein, Adam
AU - Tilley, Drake H
AU - Williams, Alan
AU - McClenathan, Bruce
AU - Collins, Limone
AU - Spooner, Christina
AU - Seshadri, Srihari
AU - Fries, Anthony
AU - Maves, Ryan
AU - Powers, John H
AU - O'Connell, Robert J
AU - Pollett, Simon D
AU - Simons, Mark P
AU - Coles, Christian L
AU - Burgess, Timothy H
N1 - Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.
PY - 2025/9/18
Y1 - 2025/9/18
N2 - BACKGROUND: Influenza is a major cause of morbidity and mortality worldwide. The Pragmatic Assessment of Influenza Vaccine Effectiveness (VE) in the Department of Defense (PAIVED) study compared the relative VE (rVE) of two licensed influenza vaccines (cell-culture-based inactivated influenza vaccine (ccIIV) and recombinant influenza vaccine (RIV)) to egg-based inactivated influenza vaccine (eIIV).METHODS: Between 2018-2021, PAIVED randomized (1:1:1) eligible Military Health System (MHS) beneficiaries to receive eIIV, ccIIV, or RIV during an influenza season. Participants received weekly surveys querying influenza-like illness (ILI); those reporting ILI completed an online symptom diary, were interviewed by research staff, and underwent nasal swab collection. Laboratory-confirmed influenza was the primary outcome. Immunogenicity assessment was conducted in a subset of participants.RESULTS: Among 15,432 participants, influenza was identified in 87/5130 (1.7%) ccIIV recipients, 79/5154 (1.5%) RIV recipients, and 69/5148 (1.3%) eIIV recipients during their season of enrollment. rVE of ccIIV compared to eIIV was -27% (95% confidence interval [CI], -73%, 8%), and rVE of RIV compared to eIIV was -14% (95% CI -58%, 17%). RIV (N=375) recipients were more likely to seroconvert (4-fold increase) than those who received eIIV (N=355) (A/H1N1: 49.1% vs 29.0%; A/H3N2: 71.2% vs 30.4%; B/Victoria 24.5% vs 13.8%; B/Yamagata 17.1% vs 5.4%; p<0.001 for all). ccIIV (N=357) recipients were more likely to seroconvert only against A/H3N2 compared to eIIV recipients (44.0% vs 30.4%) (p<0.001).CONCLUSIONS: Significant differences in VE were not detected comparing egg-based to non-egg-based influenza vaccines, although immunogenicity differences were observed; low influenza case numbers impacted VE estimate precision.TRIAL REGISTRATION: ClinicalTrials.gov NCT03734237.
AB - BACKGROUND: Influenza is a major cause of morbidity and mortality worldwide. The Pragmatic Assessment of Influenza Vaccine Effectiveness (VE) in the Department of Defense (PAIVED) study compared the relative VE (rVE) of two licensed influenza vaccines (cell-culture-based inactivated influenza vaccine (ccIIV) and recombinant influenza vaccine (RIV)) to egg-based inactivated influenza vaccine (eIIV).METHODS: Between 2018-2021, PAIVED randomized (1:1:1) eligible Military Health System (MHS) beneficiaries to receive eIIV, ccIIV, or RIV during an influenza season. Participants received weekly surveys querying influenza-like illness (ILI); those reporting ILI completed an online symptom diary, were interviewed by research staff, and underwent nasal swab collection. Laboratory-confirmed influenza was the primary outcome. Immunogenicity assessment was conducted in a subset of participants.RESULTS: Among 15,432 participants, influenza was identified in 87/5130 (1.7%) ccIIV recipients, 79/5154 (1.5%) RIV recipients, and 69/5148 (1.3%) eIIV recipients during their season of enrollment. rVE of ccIIV compared to eIIV was -27% (95% confidence interval [CI], -73%, 8%), and rVE of RIV compared to eIIV was -14% (95% CI -58%, 17%). RIV (N=375) recipients were more likely to seroconvert (4-fold increase) than those who received eIIV (N=355) (A/H1N1: 49.1% vs 29.0%; A/H3N2: 71.2% vs 30.4%; B/Victoria 24.5% vs 13.8%; B/Yamagata 17.1% vs 5.4%; p<0.001 for all). ccIIV (N=357) recipients were more likely to seroconvert only against A/H3N2 compared to eIIV recipients (44.0% vs 30.4%) (p<0.001).CONCLUSIONS: Significant differences in VE were not detected comparing egg-based to non-egg-based influenza vaccines, although immunogenicity differences were observed; low influenza case numbers impacted VE estimate precision.TRIAL REGISTRATION: ClinicalTrials.gov NCT03734237.
U2 - 10.1093/cid/ciaf503
DO - 10.1093/cid/ciaf503
M3 - Article
C2 - 40973113
SN - 1058-4838
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
ER -