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

NCT ID: NCT01827462

Last Updated: 2017-07-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2017-03-31

Brief Summary

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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.

Detailed Description

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Participants ranging in age from 18 to 100 at time of initial enrollment will be immunized annually with the seasonal influenza vaccine, Fluzone, on Day 0. Follow-up visits will be conducted on Day 6-8 and Day 28. Unsolicited adverse events are collected from immunization until the Day 28 visit, serious adverse events are collected for the entire time of study participation. A blood sample is collected pre-immunization and at each follow-up visit. Volunteers will be followed for up to 11 years, those too frail to come in for visits received annual phone calls to monitor health. Last annual influenza vaccines were given in Fall 2015.

The main basic research effort will be to collect safety data and follow medical history events in elderly and younger control subjects. Investigators will also look at immune responses to influenza vaccination. In 2008, 2012 and 2014, the cohort added additional participants to replace those who had withdrawn.

Beginning in 2014, those participants 65 years and older were immunized with High Dose trivalent Fluzone and younger participants received the quadrivalent formulation of Fluzone.

Conditions

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Influenza

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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18-30 year olds at enrollment

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.

Group Type EXPERIMENTAL

Trivalent, inactivated influenza vaccine (TIV)

Intervention Type BIOLOGICAL

Licensed Seasonal Influenza Vaccine TIV

Quadrivalent, inactivated influenza vaccine (IIV4)

Intervention Type BIOLOGICAL

Licensed Seasonal Influenza Vaccine IIV4

60-80 year olds at enrollment

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.

Group Type EXPERIMENTAL

Trivalent, inactivated influenza vaccine (TIV)

Intervention Type BIOLOGICAL

Licensed Seasonal Influenza Vaccine TIV

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

Intervention Type BIOLOGICAL

Licensed Seasonal High-Dose Influenza Vaccine TIV

80-100 year olds at enrollment

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.

Group Type EXPERIMENTAL

Trivalent, inactivated influenza vaccine (TIV)

Intervention Type BIOLOGICAL

Licensed Seasonal Influenza Vaccine TIV

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

Intervention Type BIOLOGICAL

Licensed Seasonal High-Dose Influenza Vaccine TIV

Interventions

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Trivalent, inactivated influenza vaccine (TIV)

Licensed Seasonal Influenza Vaccine TIV

Intervention Type BIOLOGICAL

Quadrivalent, inactivated influenza vaccine (IIV4)

Licensed Seasonal Influenza Vaccine IIV4

Intervention Type BIOLOGICAL

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

Licensed Seasonal High-Dose Influenza Vaccine TIV

Intervention Type BIOLOGICAL

Other Intervention Names

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Fluzone (IM) Fluzone (IM) Fluzone High-Dose (IM)

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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
* Receipt of live, attenuated vaccine within 60 days of vaccination
* History of Guillain-Barré Syndrome
* Pregnant or lactating woman
* Use of investigational agents within 30 days prior to enrollment
* Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment
* Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Cornelia L. Dekker

Professor, Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Cornelia L Dekker, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Mark M Davis, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 23591775 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23734205 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24337376 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24367114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24981332 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25834109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26309181 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26333287 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27746093 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28092664 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28096374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25740957 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26311730 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26832412 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29410330 (View on PubMed)

Related Links

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http://iti.stanford.edu/

Stanford Institute for Immunity, Transplantation and Infection

Other Identifiers

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1U19AI090019-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

51731

Identifier Type: OTHER

Identifier Source: secondary_id

AG-NS-0792-11

Identifier Type: OTHER

Identifier Source: secondary_id

SU-03192011-7599

Identifier Type: -

Identifier Source: org_study_id

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