Evaluation of heterosubtypic immune responses in older people

ISRCTN	ISRCTN70837239
DOI	https://doi.org/10.1186/ISRCTN70837239
Protocol serial number	6155; G0700846
Sponsor	University Hospitals of Leicester NHS Trust (UK)
Funder	Medical Research Council (MRC) (UK) (ref: G0700846)

Submission date: 23/04/2010
Registration date: 23/04/2010
Last edited: 20/07/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Iain Stephenson
Scientific

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Study information

Primary study design	Interventional
Study design	Non-randomised interventional prevention trial
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
Scientific title	Evaluation of heterosubtypic immune responses in older people before and after seasonal and pandemic influenza vaccination
Study objectives	Vaccination is the principal means of combating epidemic and pandemic influenza. As vaccines induce relatively strain-specific and short-lived antibody responses, annual immunisation with regularly updated vaccine is recommended for seasonal influenza, but would not be expected to protect against a pandemic event. In clinical trials among immunologically naïve young adults, at least two doses of conventional avian influenza H5 or H9 subunit vaccine are needed to induce moderate homologous antibody responses. However, studies including older subjects have unexpectedly found that greater than 15% and 50% of people aged over 65 years have pre-vaccination neutralising antibody to influenza H5 and H9 haemagglutinin (HA) respectively. In contrast to recipients who are antibody-negative, these subjects mount a robust antibody response to single dose H5 or H9 pandemic vaccine, more consistent with responses seen following single dose seasonal influenza vaccine suggesting that they are effectively primed to at least some strains of avian influenza. It is important to have an understanding of the basis for this as it may help steer the development of vaccines that induce broader immunity. Immunological objectives: 1. To evaluate heterosubtypic neutralising antibody to influenza viruses in older people 2. To evaluate heterosubtypic neutralising antibody responses to human and non-human influenza viruses following seasonal influenza vaccine 3. To evaluate homologous and heterosubtypic neutralising antibody responses to human and non-human influenza viruses after MF59-adjuvanted H5N1 vaccine
Ethics approval(s)	Oxfordshire REC A approved on the 1st July 2008 (ref: 08/H0304/51)
Health condition(s) or problem(s) studied	Topic: Inflammatory and Immune System, Generic Health Relevance and Cross Cutting Themes, Infection; Subtopic: Infection (all Subtopics), Inflammatory and Immune System (all Subtopics); Disease: Immunology and inflammation, Age and ageing
Intervention	Subjects will receive two doses of monovalent 7.5 microgram MF59-adjuvanted H5N1 vaccine by intramuscular injection, 3 weeks apart. Subjects will also receive 45 microgram trivalent seasonal influenza vaccine, one dose by intramuscular injection.
Intervention type	Other
Primary outcome measure(s)	1. Antibody titres (geometric mean titres) and mean fold rise after vaccination at visit 2, 3, 4 and 5 2. Proportion of subjects achieving seroconversion after vaccination at visits 2, 3, 4 and 5 3. Proportion of subjects achieving seroprotection (titre of ≥1:40) after vaccination at visits 2, 3, 4 and 5
Key secondary outcome measure(s)	1. Cell mediated responses after vaccination at visit 1, 3 and 5 2. Frequency of solicited adverse reaction reported after vaccination at visits 2, 3, 4 and 5
Completion date	01/07/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	520
Key inclusion criteria	1. Healthy subjects aged greater than or equal to 18 years of age, either sex 2. Subjects willing to receive vaccine in the trial 3. Able to complete informed consent and attend study visits
Key exclusion criteria	1. Receipt of another investigational agent within 4 weeks, or before completion of the safety follow-up period in another study, whichever is longer, prior to enrolment and unwilling to refuse participation in another clinical study through the end of the study 2. Subjects who experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) within the past 7 days before Visit 1 or any visit where trial vaccination is planned 3. Subjects who experienced fever (defined as axillary temperature greater than or equal to 38.0°C) within 3 days prior to Visit 1 4. Subjects who are pregnant or breastfeeding 5. Females of childbearing potential who refuse to use an acceptable method of birth control for the duration of the study. Adequate contraception is defined as hormonal (e.g., oral, injection, transdermal patch, implant, cervical ring), barrier (e.g., condom with spermicide or diaphragm with spermicide), intrauterine device (e.g., IUD), or monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject's study entry 6. Subjects with any serious disease, such as: 6.1. Cancer 6.2. Autoimmune disease (including rheumatoid arthritis) 6.3. Progressive chronic pulmonary disease (stable controlled respiratory disease including asthma is allowed) 6.4. Acute or progressive hepatic disease 6.5. Acute or progressive renal disease 7. Subjects for whom elective surgery is planned during the study period 8. Subjects with bleeding diathesis 9. Subjects with hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccine 10. Subjects with a history of any neurological symptoms or signs, or anaphylactic shock following administration of any vaccine 11. Subjects with known or suspected impairment/alteration of immune function, for example, resulting from: 11.1. Receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy) 11.2. Receipt of immunostimulants 11.3. Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Visit 1 or planned during the full length of the study 11.4. High risk for developing an immunocompromising disease 12. Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination 13. Subjects with a history of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives 14. Subjects with any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives
Date of first enrolment	15/08/2009
Date of final enrolment	01/07/2010

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Leicester Royal Infirmary

Leicester
LE1 5WW
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

20/07/2016: No publications found, verifying study status with principal investigator