Comparison of Immune Responses to Influenza Vaccine In Adults of Different Ages (SLVP015 2007-2017)

NCT01827462 | Completed Phase 4 Results

• 4 other identifiers: SU-03192011-75991U19AI090019-0151731AG-NS-0792-11
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators are trying to understand how immune function declines in the elderly using annual influenza vaccinations as a model system. The longitudinal study began in 2007 and continued through early 2017.

Conditions

Influenza

Keywords

Inactivated, trivalent influenza vaccine; elderly; immunosenescence; longitudinal study; Inactivated, High-Dose trivalent influenza vaccine; Inactivated, quadrivalent influenza vaccine; young adults

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Received the Influenza Vaccine

  Day 0 annually while on study

Secondary Outcomes (1)

• Number of Participants With Related Adverse Events

  Day 0 to Day 28 following each annual vaccination while on study

Other Outcomes (2)

• Evaluate Changes in Cytokine Profile in the Immune Response From Day 0 to Day 5-7 for T Cells and Antibody-secreting Cells (ASCs)

  Day 0 to 7

• Evaluate Changes in Cytokine Profile in the Immune Response From Day 0 to Day 28-32 for Responses to the Vaccine Antigens

  Day 0-Day28

Study Arms (3)

18-30 year olds at enrollment

EXPERIMENTAL

Licensed seasonal Fluzone (inactivated influenza vaccine): Trivalent, inactivated influenza vaccine (TIV) was given through the 2013-2014 season. Beginning with 2014-2015 season, Quadrivalent, inactivated influenza vaccine (IIV4) was given.

Biological: Trivalent, inactivated influenza vaccine (TIV); Biological: Quadrivalent, inactivated influenza vaccine (IIV4)

60-80 year olds at enrollment

EXPERIMENTAL

Licensed seasonal Fluzone (inactivated influenza vaccine): Trivalent, inactivated influenza vaccine (TIV) was given through the 2013-2014 season. Beginning with 2014-2015 season, High-Dose trivalent, inactivated influenza vaccine (TIV High-Dose) was given.

Biological: Trivalent, inactivated influenza vaccine (TIV); Biological: High-Dose Trivalent, inactivated influenza vaccine (TIV High-Dose)

80-100 year olds at enrollment

EXPERIMENTAL

Licensed seasonal Fluzone (inactivated influenza vaccine): Trivalent, inactivated influenza vaccine (TIV) was given through the 2013-2014 season. Beginning with 2014-2015 season, High-Dose trivalent, inactivated influenza vaccine (TIV High-Dose) was given.

Biological: Trivalent, inactivated influenza vaccine (TIV); Biological: High-Dose Trivalent, inactivated influenza vaccine (TIV High-Dose)

Interventions

Trivalent, inactivated influenza vaccine (TIV) BIOLOGICAL

Licensed Seasonal Influenza Vaccine TIV

Also known as: Fluzone (IM)

18-30 year olds at enrollment; 60-80 year olds at enrollment; 80-100 year olds at enrollment

Quadrivalent, inactivated influenza vaccine (IIV4) BIOLOGICAL

Licensed Seasonal Influenza Vaccine IIV4

Also known as: Fluzone (IM)

18-30 year olds at enrollment

High-Dose Trivalent, inactivated influenza vaccine (TIV High-Dose) BIOLOGICAL

Licensed Seasonal High-Dose Influenza Vaccine TIV

Also known as: Fluzone High-Dose (IM)

60-80 year olds at enrollment; 80-100 year olds at enrollment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-30, 60-79, or 80-100 years, inclusive at time of initial enrollment
• General good health and ambulatory at time of enrollment
• No acute illness at time of vaccination
• Willing and able to sign Informed Consent
• Available for follow-up for the planned duration of the study
• Acceptable medical history by screening evaluation and brief clinical assessment
• All female subjects of childbearing potential must use an acceptable method of contraception and not become pregnant for the duration of the clinical phase of the study (approximately 1 month to completion of Visit 3). (Acceptable contraception may include implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).

You may not qualify if:

• Prior off-study vaccination with trivalent or quadrivalent (depending no year) influenza vaccine (TIV or IIV4) or live attenuated influenza vaccine (LAIV) in the current flu season
• Allergy to egg or egg products
• Allergy to vaccine components, including thimerosal
• Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
• History of immunodeficiency
• Any chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• Blood pressure \>150 systolic or \> 95 diastolic at Visit 1
• Chronic Hepatitis B or C.
• Recent or current use of systemic immunosuppressive medication, including glucocorticoids (corticosteroid nasal sprays and inhaled steroids are permissible). Use of oral steroids (\<20mg prednisone-equivalent/day) may be acceptable after review by the investigator.
• Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• History of blood dyscrasias or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
• Use of anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin, Plavix, Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety.
• Receipt of blood or blood products within the past 6 months
• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol
• Receipt of inactivated vaccine within 14 days prior to vaccination

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (15)

• Furman D, Jojic V, Kidd B, Shen-Orr S, Price J, Jarrell J, Tse T, Huang H, Lund P, Maecker HT, Utz PJ, Dekker CL, Koller D, Davis MM. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness. Mol Syst Biol. 2013 Apr 16;9:659. doi: 10.1038/msb.2013.15.

  PMID: 23591775 BACKGROUND

• Price JV, Jarrell JA, Furman D, Kattah NH, Newell E, Dekker CL, Davis MM, Utz PJ. Characterization of influenza vaccine immunogenicity using influenza antigen microarrays. PLoS One. 2013 May 29;8(5):e64555. doi: 10.1371/journal.pone.0064555. Print 2013.

  PMID: 23734205 BACKGROUND

• Wang C, Liu Y, Xu LT, Jackson KJ, Roskin KM, Pham TD, Laserson J, Marshall EL, Seo K, Lee JY, Furman D, Koller D, Dekker CL, Davis MM, Fire AZ, Boyd SD. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol. 2014 Jan 15;192(2):603-11. doi: 10.4049/jimmunol.1301384. Epub 2013 Dec 11.

  PMID: 24337376 BACKGROUND

• Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiebaut R, Tibshirani RJ, Davis MM. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):869-74. doi: 10.1073/pnas.1321060111. Epub 2013 Dec 23.

  PMID: 24367114 BACKGROUND

• Jackson KJ, Liu Y, Roskin KM, Glanville J, Hoh RA, Seo K, Marshall EL, Gurley TC, Moody MA, Haynes BF, Walter EB, Liao HX, Albrecht RA, Garcia-Sastre A, Chaparro-Riggers J, Rajpal A, Pons J, Simen BB, Hanczaruk B, Dekker CL, Laserson J, Koller D, Davis MM, Fire AZ, Boyd SD. Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements. Cell Host Microbe. 2014 Jul 9;16(1):105-14. doi: 10.1016/j.chom.2014.05.013. Epub 2014 Jun 26.

  PMID: 24981332 BACKGROUND

• Furman D, Jojic V, Sharma S, Shen-Orr SS, Angel CJ, Onengut-Gumuscu S, Kidd BA, Maecker HT, Concannon P, Dekker CL, Thomas PG, Davis MM. Cytomegalovirus infection enhances the immune response to influenza. Sci Transl Med. 2015 Apr 1;7(281):281ra43. doi: 10.1126/scitranslmed.aaa2293.

  PMID: 25834109 BACKGROUND

• Looney TJ, Lee JY, Roskin KM, Hoh RA, King J, Glanville J, Liu Y, Pham TD, Dekker CL, Davis MM, Boyd SD. Human B-cell isotype switching origins of IgE. J Allergy Clin Immunol. 2016 Feb;137(2):579-586.e7. doi: 10.1016/j.jaci.2015.07.014. Epub 2015 Aug 22.

  PMID: 26309181 BACKGROUND

• Haddon DJ, Jarrell JA, Diep VK, Wand HE, Price JV, Tangsombatvisit S, Credo GM, Mackey S, Dekker CL, Baechler EC, Liu CL, Varma M, Utz PJ. Mapping epitopes of U1-70K autoantibodies at single-amino acid resolution. Autoimmunity. 2015;48(8):513-23. doi: 10.3109/08916934.2015.1077233. Epub 2015 Aug 31.

  PMID: 26333287 BACKGROUND

• Shen-Orr SS, Furman D, Kidd BA, Hadad F, Lovelace P, Huang YW, Rosenberg-Hasson Y, Mackey S, Grisar FA, Pickman Y, Maecker HT, Chien YH, Dekker CL, Wu JC, Butte AJ, Davis MM. Defective Signaling in the JAK-STAT Pathway Tracks with Chronic Inflammation and Cardiovascular Risk in Aging Humans. Cell Syst. 2016 Oct 26;3(4):374-384.e4. doi: 10.1016/j.cels.2016.09.009. Epub 2016 Oct 13.

  PMID: 27746093 BACKGROUND

• Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Dechanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med. 2017 Feb;23(2):174-184. doi: 10.1038/nm.4267. Epub 2017 Jan 16.

  PMID: 28092664 BACKGROUND

• de Bourcy CF, Angel CJ, Vollmers C, Dekker CL, Davis MM, Quake SR. Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1105-1110. doi: 10.1073/pnas.1617959114. Epub 2017 Jan 17.

  PMID: 28096374 BACKGROUND

• Kay AW, Bayless NL, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Blish CA. Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine. J Infect Dis. 2015 Sep 15;212(6):861-70. doi: 10.1093/infdis/jiv138. Epub 2015 Mar 4.

  PMID: 25740957 BACKGROUND

• Roskin KM, Simchoni N, Liu Y, Lee JY, Seo K, Hoh RA, Pham T, Park JH, Furman D, Dekker CL, Davis MM, James JA, Nadeau KC, Cunningham-Rundles C, Boyd SD. IgH sequences in common variable immune deficiency reveal altered B cell development and selection. Sci Transl Med. 2015 Aug 26;7(302):302ra135. doi: 10.1126/scitranslmed.aab1216.

  PMID: 26311730 BACKGROUND

• Fang F, Yu M, Cavanagh MM, Hutter Saunders J, Qi Q, Ye Z, Le Saux S, Sultan W, Turgano E, Dekker CL, Tian L, Weyand CM, Goronzy JJ. Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals. Cell Rep. 2016 Feb 9;14(5):1218-1231. doi: 10.1016/j.celrep.2016.01.002. Epub 2016 Jan 28.

  PMID: 26832412 BACKGROUND

• Ju CH, Blum LK, Kongpachith S, Lingampalli N, Mao R, Brodin P, Dekker CL, Davis MM, Robinson WH. Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains. Clin Immunol. 2018 Aug;193:70-79. doi: 10.1016/j.clim.2018.01.011. Epub 2018 Feb 2.

  PMID: 29410330 DERIVED

Related Links

• Stanford Institute for Immunity, Transplantation and Infection

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr Cornelia Dekker
• Organization: Stanford University School of Medicine, Dept. of Pediatrics

cdekker@stanford.edu

650-724-4437

Study Officials

• Cornelia L Dekker, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Mark M Davis, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Pediatrics

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: April 9, 2013
• Study Start: October 1, 2007
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2017
• Last Updated: July 11, 2017
• Results First Posted: June 12, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)