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

Rhonda E. Colombo; Stephanie A. Richard; Kat Schmidt; Christina Schofield; Anuradha Ganesan; Wesley Campbell; David Hrncir; Tahaniyat Lalani; Katrin Mende; Ana E. Markelz; Catherine M. Berjohn; Laurie Housel; Dorothy Becher; Elizabeth R. Zell; Daniel Ewing; Appavu K. Sundaram; Jitendrakumar R. Modi; Adam Saperstein; Drake H. Tilley; Alan Williams; Bruce McClenathan; Limone Collins; Christina Spooner; Srihari Seshadri; Anthony Fries; Ryan C. Maves; John H. Powers; Robert J. O’Connell; Simon D. Pollett; Mark P. Simons; Christian L. Coles; Timothy H. Burgess; B. Clakley; A. E. Markelz; K. Mende; S. Merritt; T. Merritt; A. McClung; C. Murillo; D. Nall; S. Bazan; A. Swarthout-Ebarb; D. Becher; K. Blankenship; R. Bowers; C. Coles; M. Fritschlanski; M. Grance; N. Moreno; C. Olsen; O. Ortega; H. Park; E. Parmelee; S. Pollett; S. Richard; J. Rothenberg; K. Schmidt; C. Baker; J. Bowman; A. Cochran; S. Chambers; R. Colombo; B. Jones; M. Heilweil; A. King; M. Martin; C. Schofield; S. Banks; J. McNiff; R. Smith; M. Romero; J. Dunham; T. Lalani; R. Tant; M. Cerroni; A. Austin; T. Warkentien; C. Berjohn; K. Gyben; N. Kirkland; D. Larson; R. Maves; G. Utz; G. Zollicoffer; C. Friend; J. Modi; A. Saperstein; D. Tilley; M. Wayman; T. Burgess; L. Kosh; R. J. O'Connell; M. Simons; A. Williams; A. Fries; V. Hogan; S. Purves; I. Barahona; A. Ganesan; J. Jefferson; L. Lawson; S. Loo; S. Loy; M. Macisaac; W. Campbell; L. Collins; L. Housel; S. Seshadri; C. Spooner; D. Hrncir; B. McClenathan; J. Brunader; C. Lohsl; E. Hall; L. Gazlay; C. Marrier; S. Bedno; A. Farmer; A. Nivens; G. Collins; M. Hussain; D. Turner; M. Richardson; J. Ritschl; A. Smith; D. Crosby; J. Simon; K. Matthews; C. Armstrong; D. Parish; J. Powers

doi:10.1093/cid/ciaf503

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

Rhonda E. Colombo
, Stephanie A. Richard
, Kat Schmidt
, Christina Schofield
, Anuradha Ganesan
, Wesley Campbell
, David Hrncir
, Tahaniyat Lalani
, Katrin Mende
, Ana E. Markelz
, Catherine M. Berjohn
, Laurie Housel
, Dorothy Becher
, Elizabeth R. Zell
, Daniel Ewing
, Appavu K. Sundaram
, Jitendrakumar R. Modi
, Adam Saperstein
, Drake H. Tilley
, Alan Williams

Bruce McClenathan, Limone Collins, Christina Spooner, Srihari Seshadri, Anthony Fries, Ryan C. Maves, John H. Powers, Robert J. O’Connell, Simon D. Pollett, Mark P. Simons, Christian L. Coles, Timothy H. Burgess, B. Clakley, A. E. Markelz, K. Mende, S. Merritt, T. Merritt, A. McClung, C. Murillo, D. Nall, S. Bazan, A. Swarthout-Ebarb, D. Becher, K. Blankenship, R. Bowers, C. Coles, M. Fritschlanski, M. Grance, N. Moreno, C. Olsen, O. Ortega, H. Park, E. Parmelee, S. Pollett, S. Richard, J. Rothenberg, K. Schmidt, C. Baker, J. Bowman, A. Cochran, S. Chambers, R. Colombo, B. Jones, M. Heilweil, A. King, M. Martin, C. Schofield, S. Banks, J. McNiff, R. Smith, M. Romero, J. Dunham, T. Lalani, R. Tant, M. Cerroni, A. Austin, T. Warkentien, C. Berjohn, K. Gyben, N. Kirkland, D. Larson, R. Maves, G. Utz, G. Zollicoffer, C. Friend, J. Modi, A. Saperstein, D. Tilley, M. Wayman, T. Burgess, L. Kosh, R. J. O'Connell, M. Simons, A. Williams, A. Fries, V. Hogan, S. Purves, I. Barahona, A. Ganesan, J. Jefferson, L. Lawson, S. Loo, S. Loy, M. Macisaac, W. Campbell, L. Collins, L. Housel, S. Seshadri, C. Spooner, D. Hrncir, B. McClenathan, J. Brunader, C. Lohsl, E. Hall, L. Gazlay, C. Marrier, S. Bedno, A. Farmer, A. Nivens, G. Collins, M. Hussain, D. Turner, M. Richardson, J. Ritschl, A. Smith, D. Crosby, J. Simon, K. Matthews, C. Armstrong, D. Parish, J. Powers

Biostatistics

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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 2 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 and 2021, PAIVED randomized (1:1:1) eligible Military Health System 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 <.001 for all). ccIIV (N = 357) recipients were more likely to seroconvert only against A/H3N2 compared with eIIV recipients (44.0% vs 30.4%) (P <.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.

Original language	English (US)
Pages (from-to)	e454-e463
Journal	Clinical Infectious Diseases
Volume	81
Issue number	5
DOIs	https://doi.org/10.1093/cid/ciaf503
State	Published - Nov 15 2025

Bibliographical note

Publisher Copyright:
© Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

immunogenicity
influenza
influenza-like illness
symptoms
vaccine

PubMed: MeSH publication types

Clinical Trial, Phase IV
Comparative Study
Journal Article
Multicenter Study
Pragmatic Clinical Trial
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1093/cid/ciaf503

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Colombo, R. E., Richard, S. A., Schmidt, K., Schofield, C., Ganesan, A., Campbell, W., Hrncir, D., Lalani, T., Mende, K., Markelz, A. E., Berjohn, C. M., Housel, L., Becher, D., Zell, E. R., Ewing, D., Sundaram, A. K., Modi, J. R., Saperstein, A., Tilley, D. H., ... Powers, J. (2025). 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. Clinical Infectious Diseases, 81(5), e454-e463. https://doi.org/10.1093/cid/ciaf503

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. / Colombo, Rhonda E.; Richard, Stephanie A.; Schmidt, Kat et al.
In: Clinical Infectious Diseases, Vol. 81, No. 5, 15.11.2025, p. e454-e463.

Research output: Contribution to journal › Article › peer-review

Colombo, RE, Richard, SA, Schmidt, K, Schofield, C, Ganesan, A, Campbell, W, Hrncir, D, Lalani, T, Mende, K, Markelz, AE, Berjohn, CM, Housel, L, Becher, D, Zell, ER, Ewing, D, Sundaram, AK, Modi, JR, Saperstein, A, Tilley, DH, Williams, A, McClenathan, B, Collins, L, Spooner, C, Seshadri, S, Fries, A, Maves, RC, Powers, JH, O’Connell, RJ, Pollett, SD, Simons, MP, Coles, CL, Burgess, TH, Clakley, B, Markelz, AE, Mende, K, Merritt, S, Merritt, T, McClung, A, Murillo, C, Nall, D, Bazan, S, Swarthout-Ebarb, A, Becher, D, Blankenship, K, Bowers, R, Coles, C, Fritschlanski, M, Grance, M, Moreno, N, Olsen, C, Ortega, O, Park, H, Parmelee, E, Pollett, S, Richard, S, Rothenberg, J, Schmidt, K, Baker, C, Bowman, J, Cochran, A, Chambers, S, Colombo, R, Jones, B, Heilweil, M, King, A, Martin, M, Schofield, C, Banks, S, McNiff, J, Smith, R, Romero, M, Dunham, J, Lalani, T, Tant, R, Cerroni, M, Austin, A, Warkentien, T, Berjohn, C, Gyben, K, Kirkland, N, Larson, D, Maves, R, Utz, G, Zollicoffer, G, Friend, C, Modi, J, Saperstein, A, Tilley, D, Wayman, M, Burgess, T, Kosh, L, O'Connell, RJ, Simons, M, Williams, A, Fries, A, Hogan, V, Purves, S, Barahona, I, Ganesan, A, Jefferson, J, Lawson, L, Loo, S, Loy, S, Macisaac, M, Campbell, W, Collins, L, Housel, L, Seshadri, S, Spooner, C, Hrncir, D, McClenathan, B, Brunader, J, Lohsl, C, Hall, E, Gazlay, L, Marrier, C, Bedno, S, Farmer, A, Nivens, A, Collins, G, Hussain, M, Turner, D, Richardson, M, Ritschl, J, Smith, A, Crosby, D, Simon, J, Matthews, K, Armstrong, C, Parish, D & Powers, J 2025, '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', Clinical Infectious Diseases, vol. 81, no. 5, pp. e454-e463. https://doi.org/10.1093/cid/ciaf503

Colombo RE, Richard SA, Schmidt K, Schofield C, Ganesan A, Campbell W et al. 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. Clinical Infectious Diseases. 2025 Nov 15;81(5):e454-e463. doi: 10.1093/cid/ciaf503

Colombo, Rhonda E. ; Richard, Stephanie A. ; Schmidt, Kat et al. / 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. In: Clinical Infectious Diseases. 2025 ; Vol. 81, No. 5. pp. e454-e463.

@article{46a0a17fff0b4d23a6f0ad7687bc8486,

title = "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",

abstract = "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 2 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 and 2021, PAIVED randomized (1:1:1) eligible Military Health System 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 <.001 for all). ccIIV (N = 357) recipients were more likely to seroconvert only against A/H3N2 compared with eIIV recipients (44.0\% vs 30.4\%) (P <.001). Conclusions Significant differences in VE were not detected comparing egg-based to non-egg{\textendash}based influenza vaccines, although immunogenicity differences were observed; low influenza case numbers impacted VE estimate precision. Trial Registration ClinicalTrials.gov NCT03734237.",

keywords = "immunogenicity, influenza, influenza-like illness, symptoms, vaccine",

author = "Colombo, \{Rhonda E.\} and Richard, \{Stephanie A.\} and Kat Schmidt and Christina Schofield and Anuradha Ganesan and Wesley Campbell and David Hrncir and Tahaniyat Lalani and Katrin Mende and Markelz, \{Ana E.\} and Berjohn, \{Catherine M.\} and Laurie Housel and Dorothy Becher and Zell, \{Elizabeth R.\} and Daniel Ewing and Sundaram, \{Appavu K.\} and Modi, \{Jitendrakumar R.\} and Adam Saperstein and Tilley, \{Drake H.\} and Alan Williams and Bruce McClenathan and Limone Collins and Christina Spooner and Srihari Seshadri and Anthony Fries and Maves, \{Ryan C.\} and Powers, \{John H.\} and O{\textquoteright}Connell, \{Robert J.\} and Pollett, \{Simon D.\} and Simons, \{Mark P.\} and Coles, \{Christian L.\} and Burgess, \{Timothy H.\} and B. Clakley and Markelz, \{A. E.\} and K. Mende and S. Merritt and T. Merritt and A. McClung and C. Murillo and D. Nall and S. Bazan and A. Swarthout-Ebarb and D. Becher and K. Blankenship and R. Bowers and C. Coles and M. Fritschlanski and M. Grance and N. Moreno and C. Olsen and O. Ortega and H. Park and E. Parmelee and S. Pollett and S. Richard and J. Rothenberg and K. Schmidt and C. Baker and J. Bowman and A. Cochran and S. Chambers and R. Colombo and B. Jones and M. Heilweil and A. King and M. Martin and C. Schofield and S. Banks and J. McNiff and R. Smith and M. Romero and J. Dunham and T. Lalani and R. Tant and M. Cerroni and A. Austin and T. Warkentien and C. Berjohn and K. Gyben and N. Kirkland and D. Larson and R. Maves and G. Utz and G. Zollicoffer and C. Friend and J. Modi and A. Saperstein and D. Tilley and M. Wayman and T. Burgess and L. Kosh and O'Connell, \{R. J.\} and M. Simons and A. Williams and A. Fries and V. Hogan and S. Purves and I. Barahona and A. Ganesan and J. Jefferson and L. Lawson and S. Loo and S. Loy and M. Macisaac and W. Campbell and L. Collins and L. Housel and S. Seshadri and C. Spooner and D. Hrncir and B. McClenathan and J. Brunader and C. Lohsl and E. Hall and L. Gazlay and C. Marrier and S. Bedno and A. Farmer and A. Nivens and G. Collins and M. Hussain and D. Turner and M. Richardson and J. Ritschl and A. Smith and D. Crosby and J. Simon and K. Matthews and C. Armstrong and D. Parish and J. Powers",

note = "Publisher Copyright: {\textcopyright} Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.",

year = "2025",

month = nov,

day = "15",

doi = "10.1093/cid/ciaf503",

language = "English (US)",

volume = "81",

pages = "e454--e463",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "5",

}

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 - 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, Daniel

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 C.

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.

AU - Clakley, B.

AU - Markelz, A. E.

AU - Mende, K.

AU - Merritt, S.

AU - Merritt, T.

AU - McClung, A.

AU - Murillo, C.

AU - Nall, D.

AU - Bazan, S.

AU - Swarthout-Ebarb, A.

AU - Becher, D.

AU - Blankenship, K.

AU - Bowers, R.

AU - Coles, C.

AU - Fritschlanski, M.

AU - Grance, M.

AU - Moreno, N.

AU - Olsen, C.

AU - Ortega, O.

AU - Park, H.

AU - Parmelee, E.

AU - Pollett, S.

AU - Richard, S.

AU - Rothenberg, J.

AU - Schmidt, K.

AU - Baker, C.

AU - Bowman, J.

AU - Cochran, A.

AU - Chambers, S.

AU - Colombo, R.

AU - Jones, B.

AU - Heilweil, M.

AU - King, A.

AU - Martin, M.

AU - Schofield, C.

AU - Banks, S.

AU - McNiff, J.

AU - Smith, R.

AU - Romero, M.

AU - Dunham, J.

AU - Lalani, T.

AU - Tant, R.

AU - Cerroni, M.

AU - Austin, A.

AU - Warkentien, T.

AU - Berjohn, C.

AU - Gyben, K.

AU - Kirkland, N.

AU - Larson, D.

AU - Maves, R.

AU - Utz, G.

AU - Zollicoffer, G.

AU - Friend, C.

AU - Modi, J.

AU - Saperstein, A.

AU - Tilley, D.

AU - Wayman, M.

AU - Burgess, T.

AU - Kosh, L.

AU - O'Connell, R. J.

AU - Simons, M.

AU - Williams, A.

AU - Fries, A.

AU - Hogan, V.

AU - Purves, S.

AU - Barahona, I.

AU - Ganesan, A.

AU - Jefferson, J.

AU - Lawson, L.

AU - Loo, S.

AU - Loy, S.

AU - Macisaac, M.

AU - Campbell, W.

AU - Collins, L.

AU - Housel, L.

AU - Seshadri, S.

AU - Spooner, C.

AU - Hrncir, D.

AU - McClenathan, B.

AU - Brunader, J.

AU - Lohsl, C.

AU - Hall, E.

AU - Gazlay, L.

AU - Marrier, C.

AU - Bedno, S.

AU - Farmer, A.

AU - Nivens, A.

AU - Collins, G.

AU - Hussain, M.

AU - Turner, D.

AU - Richardson, M.

AU - Ritschl, J.

AU - Smith, A.

AU - Crosby, D.

AU - Simon, J.

AU - Matthews, K.

AU - Armstrong, C.

AU - Parish, D.

AU - Powers, J.

N1 - Publisher Copyright: © Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.

PY - 2025/11/15

Y1 - 2025/11/15

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 2 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 and 2021, PAIVED randomized (1:1:1) eligible Military Health System 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 <.001 for all). ccIIV (N = 357) recipients were more likely to seroconvert only against A/H3N2 compared with eIIV recipients (44.0% vs 30.4%) (P <.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 2 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 and 2021, PAIVED randomized (1:1:1) eligible Military Health System 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 <.001 for all). ccIIV (N = 357) recipients were more likely to seroconvert only against A/H3N2 compared with eIIV recipients (44.0% vs 30.4%) (P <.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.

KW - immunogenicity

KW - influenza

KW - influenza-like illness

KW - symptoms

KW - vaccine

UR - https://www.scopus.com/pages/publications/105025774353

UR - https://www.scopus.com/pages/publications/105025774353#tab=citedBy

U2 - 10.1093/cid/ciaf503

DO - 10.1093/cid/ciaf503

M3 - Article

C2 - 40973113

AN - SCOPUS:105025774353

SN - 1058-4838

VL - 81

SP - e454-e463

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 5

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

PubMed: MeSH publication types

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