Influenza Vaccine in Lung Transplant Patients - Antibody

Effect of Annual Influenza Immunization on Antibody Response in Lung Transplant Patients

This is a sub-study of a 5-year study designed to investigate how antibody and T cell responses following influenza vaccine compare among lung transplant patients, patients waiting for lung transplantation, and healthy individuals.

This prospective, parallel study was done to investigate the responses to influenza vaccine in consecutive years.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Influenza vaccine

Detailed Description

Lung transplant patients may be at an incrementally higher risk of influenza infection than other transplant patients. Factors that predispose them to respiratory infection include high degree of immunosuppression, altered mucociliary clearance, repeated airway instrumentation, bronchial anastomotic obstruction, disruption of lymphatic drainage, and the exposure of the transplanted organ to the environment.

The influenza vaccine used for those at high risk for influenza morbidity and mortality is an inactivated trivalent preparation. Influenza vaccine contains 2 type A viruses and 1 type B virus. The vaccine is reformulated each year based on the viruses expected to circulate during the upcoming season. A protective antibody response to influenza vaccine is considered an antibody titer of at least 1:40. Seroconversion following influenza immunization implies at least a 4-fold increase in antibody concentrations. Although these indicators of a positive response to influenza immunization have significant overlap, they are not exactly the same. One must consider that a person may have antibodies before immunization because of previous exposure to a vaccine virus or an antigenically similar influenza strain.

Seroconversion rates following influenza vaccination are lower in lung transplant patients than in healthy persons. Clearly, immunization elicits an antibody response in this population, but the response is not as vigorous as in immunocompetent persons. It has been demonstrated that only the B/HongKong virus was associated with a lower seroconversion rate, and this virus was the only one to change from the previous year's vaccine. Seroconversion rates decrease with subsequent exposure to the same influenza vaccine viruses, but seroprotection rates remain the same. It is conceivable that the seroconversion response is more affected by immunosuppression than is the seroprotection response. Stated another way, the ability to mount a high spike in antibody production is hindered. It is difficult to fully ascertain the exact degree of immune impairment in lung transplant recipients because both studies investigating influenza vaccine response used healthy persons as the comparison group. Healthy persons may have less experience with influenza vaccine than do persons with severe respiratory conditions. An immunologically naive host is more likely to mount the large change in antibody concentration and increase the likelihood of seroconversion. Therefore, patients waiting for lung transplantation were used as a comparison group.

This prospective, parallel study was done to investigate the responses to influenza vaccine in consecutive years. All participants had a blood sample taken for measurement of influenza antibody titers before receiving the influenza vaccine. Subsequently, the 2004-2005-A/New Caledonia/20/99(H1N1)-like, A/Wyoming/3/2003(H3N2), and B/Shanghai/361/2002-like antigens-and/or 2005-2006-A/New Caledonia/ 20/00(H1N1)-like, A/California/7/2004 (H3N2)-like, and B/Shanghai/361/2002-like antigens-influenza vaccine was administered intramuscularly. Serum was stored at -80°C until the day of analysis. A second blood sample was obtained 2 to 4 weeks later to measure antibody response.

[This substudy that was originally registered to NCT00205270 and subsequently registered to its own NCT number for the purpose of clarity in linked results]

• Study Type: Observational
• Enrollment (Actual): 122

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy adults, or patients receiving care pre- or post-lung transplant at University of Wisconsin Hospital

Description

Inclusion Criteria:

• Receiving care pre- or post-lung transplant at University of Wisconsin Hospital
• Healthy adult

Exclusion Criteria:

• Allergy to eggs
• Moderate to severe febrile illness
• Active treatment for acute rejection
• Received season's influenza vaccine prior to enrollment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vaccine, pre-transplant; cohort consists of individuals waiting for lung transplantation. Inactivated influenza vaccine will be administered intramuscularly annually.	Drug: Influenza vaccine; influenza vaccine 0.5 ml intramuscularly each season 2004-2005 season antigens: A/New Caledonia/20/99(H1N1)-like, A/Wyoming/3/2003(H3N2), and B/Shanghai/361/2002-like antigens 2005-2006 season antigens: A/New Caledonia/ 20/00(H1N1)-like, A/California/7/2004 (H3N2)-like, and B/Shanghai/361/2002-like antigens
Vaccine, post-transplant; Cohort consist of individuals who have received lung transplants Inactivated influenza vaccine will be administered intramuscularly annually.	Drug: Influenza vaccine; influenza vaccine 0.5 ml intramuscularly each season 2004-2005 season antigens: A/New Caledonia/20/99(H1N1)-like, A/Wyoming/3/2003(H3N2), and B/Shanghai/361/2002-like antigens 2005-2006 season antigens: A/New Caledonia/ 20/00(H1N1)-like, A/California/7/2004 (H3N2)-like, and B/Shanghai/361/2002-like antigens
Vaccine, not receiving transplant; Cohort consists of healthy individuals who received the influenza vaccine Inactivated influenza vaccine will be administered intramuscularly annually.	Drug: Influenza vaccine; influenza vaccine 0.5 ml intramuscularly each season 2004-2005 season antigens: A/New Caledonia/20/99(H1N1)-like, A/Wyoming/3/2003(H3N2), and B/Shanghai/361/2002-like antigens 2005-2006 season antigens: A/New Caledonia/ 20/00(H1N1)-like, A/California/7/2004 (H3N2)-like, and B/Shanghai/361/2002-like antigens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Log-transformed change in Antibody Responses	Influenza antibody concentrations are measured by HIA in samples taken before immunization and 2 to 4 weeks later. Antibody response is the difference in serum concentrations from before and 2 to 4 weeks after vaccination. Antibody concentrations were compared between seasons by using a Wilcoxon rank sum test.	baseline, 2-4 weeks post-vaccination (2004-2005 season), up to 1 year, up to 1 year and 4 weeks (2005-2006 season)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Seroconversion	Seroconversion was defined as more than a 4-fold increase in serum hemagglutination units (HAU).	2-4 weeks post-vaccination (2004-2005 season), up to 1 year and 4 weeks (post-vaccination 2005-2006 season)
Incidence of Seroprotection	Seroprotection was defined as an antibody concentration of 40 HAU or greater.	baseline, 2-4 weeks post-vaccination (2004-2005 season), up to 1 year, up to 1 year and 4 weeks (2005-2006 season)
Correlation of Time Since Transplantation to Antibody Response in Lung Transplant Patients	Time since transplant was correlated to antibody responses in the transplant subjects by using a Spearman correlation coefficient to determine the influence of chronic immunosuppression on immune responses. Statistical significance was defined as P less than .05.	2-4 weeks post-vaccination (2004-2005 season), up to 1 year and 4 weeks (post-vaccination 2005-2006 season)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison

Publications and helpful links

General Publications

• Dopp JM, Wiegert NA, Moran JJ, Francois ML, Radford KL, Thomas H, Love RB, Hayney MS. Effect of annual influenza immunization on antibody response in lung transplant patients. Prog Transplant. 2009 Jun;19(2):153-9. doi: 10.1177/152692480901900209.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Healthy; Pre or post-lung transplant
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: H-2004-0240b; A561000 (Other Identifier: UW Madison); PHARM/PHARMACY/PHARMACY (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No