NCT03734237: PAIVED

A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Active, enrolled Phase 4 Results posted Last updated 2 April 2026

What this trial tests

Phase 4 trial testing Egg based influenza vaccines in Influenza in 15,448 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

6 November 2018

Primary endpoint
7 July 2022

30 June 2026

Quick facts

Lead sponsor	Henry M. Jackson Foundation for the Advancement of Military Medicine
Phase	Phase 4
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	15,448
Start date	6 November 2018
Primary completion	7 July 2022
Estimated completion	30 June 2026
Sites	9 locations across United States

Drugs / interventions tested

• Egg based influenza vaccines — full drug profile →
• Recombinant influenza vaccines — full drug profile →
• Cell-culture based influenza vaccines — full drug profile →

Conditions studied

• Influenza — all drugs for Influenza →
• Influenza-like Illness — all drugs for Influenza-like Illness →
• Influenza Vaccines — all drugs for Influenza Vaccines →

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Who can join

18 and older, any sex, with Influenza or Influenza-like Illness. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Laboratory Confirmed Influenza Primary · Onset > 13 days after vaccination up to 1 year

Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.

Group	Value	95% CI
Egg-based Vaccine	69
Cell-derived Vaccine	87
Recombinant Vaccine	79

Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains. Secondary · Baseline to 21-35 days post vaccine

Strain-specific seroconversion rate determined by reference hemagglutination inhibition assay.

H1N1: Number with 4-fold rise in HI

Group	Value	95% CI
Egg-based Vaccine	103
Cell-derived Vaccine	114
Recombinant Vaccine	184

H3N2: Number with 4-fold rise in HI

Group	Value	95% CI
Egg-based Vaccine	108
Cell-derived Vaccine	157
Recombinant Vaccine	267

B-Victoria: Number with 4-fold rise in HI

Group	Value	95% CI
Egg-based Vaccine	49
Cell-derived Vaccine	48
Recombinant Vaccine	92

B-Yamagata: Number with 4-fold rise in HI

Group	Value	95% CI
Egg-based Vaccine	19
Cell-derived Vaccine	24
Recombinant Vaccine	64

Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine. Secondary · Baseline to 21-35 days post vaccine

Neutralizing antibody responses (4-fold rise) to HA-psuedoviruses corresponding to vaccine-matched viruses, recently circulating influenza virus, and emerging influenza strain.

Seroconversion rate against egg-passaged HA-pseudovirus (SGP/19/16 NIB-104)

Group	Value	95% CI
Egg Based Influenza Vaccines	8.7
Cell-derived Vaccine	13.9
Recombinant Vaccine	47.1

Seroconversion rate against cell-passaged HA-pseudovirus (NC/04/16)

Group	Value	95% CI
Egg Based Influenza Vaccines	8.7
Cell-derived Vaccine	8.3
Recombinant Vaccine	43.1

Seroconversion rate against wild-type (SGP/19/16; recombinant HA-pseudovirus)

Group	Value	95% CI
Egg Based Influenza Vaccines	4.3
Cell-derived Vaccine	16.7
Recombinant Vaccine	56.9

Seroconversion rate against HA-pseudovirus corresponding to prior season vaccine strain

Group	Value	95% CI
Egg Based Influenza Vaccines	6.5
Cell-derived Vaccine	13.9
Recombinant Vaccine	62.7

Seroconversion rate against HA-pseudovirus corresponding to recently circulating virus

Group	Value	95% CI
Egg Based Influenza Vaccines	4.3
Cell-derived Vaccine	11.1
Recombinant Vaccine	52.9

Seroconversion rate against HA-pseudovirus corresponding to emerging infuenza strain

Group	Value	95% CI
Egg Based Influenza Vaccines	2.2
Cell-derived Vaccine	0
Recombinant Vaccine	21.6

Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine. Secondary · Baseline to 21-35 days post vaccine

Anti-Neuraminidase (Anti-NA) titer responses determined by enzyme linked immuno-assay.

N1 Titer, Pre-vaccination

Group	Value	95% CI
Egg Based Influenza Vaccines	54	40.8 – 70.6
Cell-derived Vaccine	111	72.7 – 168.0
Recombinant Vaccine	80.7	58.4 – 111.5

N1 Titer, Post-vaccination

Group	Value	95% CI
Egg Based Influenza Vaccines	207	145.2 – 295.4
Cell-derived Vaccine	109	72.3 – 163.5
Recombinant Vaccine	77.7	56.8 – 106.2

N2 Titer, Pre-vaccination

Group	Value	95% CI
Egg Based Influenza Vaccines	121	93.6 – 157.1
Cell-derived Vaccine	123	82.2 – 182.7
Recombinant Vaccine	83.0	67.6 – 102.0

N2 Titer, Post-vaccination

Group	Value	95% CI
Egg Based Influenza Vaccines	292	214.3 – 396.5
Cell-derived Vaccine	226	150.4 – 338.7
Recombinant Vaccine	78.4	63.4 – 96.9

Number of Participants With Influenza-Like Illness Secondary · Onset > 13 days after vaccination up to 1 year

Rate of protocol defined influenza-like illness ascertained by participant response to active surveillance.

Group	Value	95% CI
Egg-based Influenza Vaccine	1054
Recombinant Vaccine	1121
Cell-derived Vaccine	1078

Number of Participants With SARS-CoV-2 and Influenza Co-Infection Secondary · Onset > 13 days after influenza vaccination up until one year

Laboratory-confirmed SARS CoV2, and SARS CoV2 plus influenza co-infection, as ascertained by nasal swab PCR.

SC2 Status

Group	Value	95% CI
Egg-based Vaccine	131
Recombinant Vaccine	159
Cell-derived Vaccine	140

Influenza/SC2 Coinfection Status

Group	Value	95% CI
Egg-based Vaccine	0
Recombinant Vaccine	1
Cell-derived Vaccine	1

Symptom Severity of SARS CoV2 Secondary · onset >13 days after Influenza vaccination up to 1 year

Symptom severity scores were reported by participants using FLU-PRO Plus (Influenza Patient Reported Outcomes), a standardized instrument developed to measure the intensity and frequency of viral respiratory tract symptoms. FluPRO Plus symptom scores range from 0 ("not at all") to 4 ("very much"), with higher scores indicating greater severity.

Group	Value	95% CI
Egg-based Vaccine	1.03	0.74 – 1.44
Recombinant Vaccine	1.12	0.68 – 1.50
Cell-derived Vaccine	1.11	0.71 – 1.53

Sponsor's own description

A total of 18,000 eligible subjects (or 6,000 subject distributed evenly between the 3 study arms) will be enrolled. Eligible subjects will be randomized in 1:1:1 (cell-culture-based vaccine, the recombinant vaccine, or the egg-based vaccine) over four influenza seasons (2018-2019, 2019-2020, 2020-2021, and 2021-2022).

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Challenges of Making Effective Influenza Vaccines.
   Gouma S, Anderson EM, Hensley SE. · · 2020 · cited 71× · PMID 32392457 · DOI 10.1146/annurev-virology-010320-044746
2. Summary of the National Advisory Committee on Immunization (NACI) Supplemental Statement on Recombinant Influenza Vaccines.
   Gil A, Sinilaite A, Papenburg J. · · 2022 · cited 3× · PMID 38116047 · DOI 10.14745/ccdr.v48i09a02
3. 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 RE, Richard SA, Schmidt K, Schofield C, et al · · 2025 · cited 2× · PMID 40973113 · DOI 10.1093/cid/ciaf503
4. Influenza-like illness in cigarette smokers and electronic-cigarette users: a secondary analysis from the PAIVED study.
   Jones RDC, Schmidt K, Schofield C, Ganesan A, et al · · 2026 · PMID 42077984 · DOI 10.3389/fpubh.2026.1725232
5. Healthcare Workers Have More Frequent and Less Severe Influenza-Like Illness Than Non-healthcare Workers: Findings From the PAIVED Study.
   Liberg R, Schmidt K, Schofield C, Ganesan A, et al · · 2026 · PMID 41531506 · DOI 10.1093/ofid/ofaf728