Randomized Influenza Vaccine Evaluation of Immune Response

Randomized Open-Label Trial to Compare Immunogenicity of Egg-Based and Non-Egg Based Quadrivalent Influenza Vaccines Among Adults 18-64 Years of Age (US Flu Vaccine Effectiveness Serologic Study, 2018-19 and 2019-20)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03598439

Acronym

RIVER

Enrollment

366

Registered

2018-07-26

Start date

2018-07-30

Completion date

2024-07-09

Last updated

2025-11-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza

Keywords

influenza vaccine, adults, Immune response

Brief summary

Licensed influenza vaccines are manufactured with a variety of technologies. The majority are split, inactivated vaccines derived from egg-adapted, high growth reassortant viruses. Two US licensed products do not use egg-adapted viruses: Flucelvax (mammalian cell culture) and FluBlok (recombinant). There is increasing evidence that egg propagation induces virus mutations that impair the immune responses to circulating viruses. However, the impact of egg-propagation on clinical vaccine effectiveness is uncertain, and there is no preferential recommendation for any specific influenza vaccine product or technology. A direct comparison of serologic response to egg based and non-egg based vaccines in adults has not been performed. This randomized trial will compare serologic responses to the egg- and non-egg A(H3N2) vaccine component. The study cohort will be followed for two influenza seasons to evaluate sequential vaccination effects on immune response.

Interventions

BIOLOGICALStandard IIV4

Standard inactivated influenza vaccine

BIOLOGICALRecombinant

Influenza vaccine that uses a hemagglutinin protein manufactured in insect cells with a baculovirus vector

BIOLOGICALCell-culture

inactivated influenza vaccine manufactured using mammalian cell lines; current vaccine uses a cell-propagated H3N2 strain.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 64 Years

Healthy volunteers

Inclusion criteria

* Aged 18-64 years * Marshfield Clinic patients living in or around Marshfield, Wisconsin since July 2015 * Willing and able to give informed consent and comply with study requirements

Exclusion criteria

* Receipt of 2018-19 influenza vaccine prior to study enrollment * Known to be pregnant at the time of enrollment * Current participation or plans to participate in another clinical trial involving an experimental agent * Presence of a contraindication to influenza vaccination * Plans to relocate outside the geographic location in the next two years

Design outcomes

Primary

Measure	Time frame	Description
Post-vaccination titer	28 days	geometric mean titers (as measured by microneutralization) to cell-grown A(H3N2) vaccine reference virus

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026