NCT00798343

Heterosubtypic Immune Responses to Influenza in Older People

Evaluation of Heterosubtypic Immune Responses in Older People Before and After Seasonal and Pandemic Influenza Vaccination

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 292 (actual)
• Sponsor: University Hospitals, Leicester · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

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 young adults, at least two doses of avian influenza H5 or H9 subunit vaccine are needed to induce moderate antibody responses. However, studies including older subjects have unexpectedly found that some people aged over 65 yrs have pre-vaccination neutralising antibody to influenza H5 and H9 respectively. These subjects mount a robust antibody response to single dose H5 or H9 pandemic vaccine, suggesting that they are effectively primed to at least some strains of avian influenza. This exploratory proposal focuses on those elderly subjects whose immune systems already exhibit antibodies to H5 with a goal of investigating the humoral and cellular basis of the immune response to seasonal and pandemic vaccination. We will examine neutralising antibody responses to a range of human and non-human influenza viruses before and after seasonal and pandemic vaccination and evaluate cellular B and T cell immune responses before and after pandemic H5 vaccination

Detailed description

STUDY OBJECTIVES: Immunological objectives * To evaluate heterosubtypic neutralising antibody to influenza viruses in older people * To evaluate heterosubtypic neutralising antibody responses to human and non-human influenza viruses following seasonal influenza vaccine * To evaluate homologous and heterosubtypic neutralising antibody responses to human and non-human influenza viruses after MF59-adjuvanted H5N1 vaccine; * To evaluate cellular B and T cell responses to influenza H5 in non-exposed subjects who exhibit anti-H5 neutralising antibodies before and after seasonal (TIV) or pandemic H5 vaccination * To identify epitopes on the influenza haemagglutinin to which anti-H5 neutralising antibodies in sera from non-exposed subjects are directed Safety Objectives * To evaluate safety of one or two IM doses of MF59-adjuvanted A/Vietnam/1194/2004 (H5N1) influenza vaccine, containing 7.5 μg of H5 antigen in adult subjects * To evaluate safety of one IM dose of seasonal influenza vaccine, containing 15 μg of H1, H3 and B antigen in adult subjects Hypotheses: * Heterosubtypic cross reacting antibodies to influenza exist in some elderly subjects and can be boosted by a single dose of (a) seasonal TIV or (b) pandemic influenza vaccination * Heterosubtypic cross reacting antibodies to influenza do not exist in younger subjects and cannot be induced by (a) seasonal TIV or (b) pandemic influenza vaccination

Conditions

• Influenza

Interventions

Type	Name	Description
BIOLOGICAL	Seasonal vaccine	Non-adjuvanted seasonal influenza vaccine (total dose 45ug)
BIOLOGICAL	H5 vaccine	MF59-adjuvanted A/Vietnam/1194 H5N1 vaccine 7.5ug dose

Timeline

• Start date: 2009-01-01
• Primary completion: 2010-03-01
• Completion: 2013-09-01
• First posted: 2008-11-26
• Last updated: 2014-06-03

Locations

1 site across 1 country: United Kingdom