Comparative Effectiveness and Safety of Adjuvanted and Other Influenza Vaccine Technologies Among Patients Receiving Dialysis

ABSTRACT
Annual influenza vaccination is recommended for patients with ESRD undergoing dialysis by the Advisory
Committee on Immunization Practices (ACIP). Non-experimental studies suggest that inactivated, seasonal,
standard-dose vaccines are not effective or minimally effective at reducing influenza-related hospitalizations or
mortality in the dialysis population, and the high-dose vaccine provides little to no additional protection beyond
the standard-dose vaccine for these outcomes. Two vaccine formulations using advanced technologies have
been licensed in recent years. The adjuvanted influenza vaccine, licensed in 2015, enhances the magnitude of
the immune response to vaccine antigens and broadens the response to include similar mismatched viruses
through heterotypic protection. The recombinant influenza vaccine, licensed in 2013 (trivalent) and 2017
(quadrivalent), uses the baculovirus-insect cell system to produce recombinant influenza antigens. Evidence
suggests that both the adjuvanted and recombinant influenza vaccines have higher vaccine effectiveness
compared to standard-dose vaccines in the general population. Despite increasing uptake of the adjuvanted
and recombinant influenza vaccines among the dialysis population in recent years, no large-scale studies have
been conducted to evaluate the utilization, effectiveness, or safety of these newly licensed vaccines in the
vulnerable population of patients on dialysis. A large study is needed to compare the newly licensed
adjuvanted and recombinant vaccines versus other vaccines and to inform influenza prevention approaches in
the dialysis population. We propose a large, non-experimental study using existing data from the United
States Renal Data System (USRDS) to examine the use, effectiveness, and safety of various influenza
vaccines among adult patients with ESRD undergoing dialysis. The large size of our study will allow us to
characterize small differences in vaccine effectiveness and safety between adjuvanted or recombinant
vaccines vs. standard or high-dose vaccines during the same influenza seasons. Vaccine effectiveness
analyses will incorporate a broad range of influenza-related outcomes, including markers of severity of illness.
Safety analyses will focus on a priori identified adverse events after influenza immunization. Study design and
analyses will use robust methods to measure and account for confounding bias. Our findings will inform
dialysis patients and their providers about the risks and benefits of different vaccines and influence vaccine
policy, with the ultimate goal of reducing the burden of respiratory disease in this vulnerable population.

Grant Number: 5R21AI178408-02
NIH Institute/Center: NIH
Principal Investigator: Anne Butler