Exploring Novel Mechanisms of Vaccine Failure LAIV Pilot Study

NCT02266992 | Completed Phase 2

• 1 other identifier: STH18166
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Influenza ('flu) can cause severe infections, especially in people with weakened immune systems such as those with HIV. For this reason, yearly vaccination is recommended with the standard 'inactivated' influenza vaccine to try and prevent infections in these populations. It is also recommended in all health care workers, to help prevent the spread of influenza within healthcare settings. However, having HIV infection may mean vaccines work less well in some people and the investigators do not completely understand why. An alternative to the standard 'inactivated' annual influenza vaccine is the 'live attenuated influenza vaccine' (LAIV), which means it consists of weakened versions of the influenza virus. Unlike the standard vaccine, which is given by injection, LAIV is a spray that is given into each nostril. It is now given to children in the UK in preference to the standard vaccine as it results in greater protection from influenza. In some other countries, like the USA, adults are also given LAIV, where it seems to work just as well as the standard vaccine. A few studies in the past have shown that LAIV is safe and effective in HIVinfected children and adults. The investigators want to give LAIV to HIVinfected and HIV negative individuals, to try to find out new information about how HIV infection may change the way in which people respond to vaccines. The investigators will do this by comparing both the early genetic response to the vaccines and later responses from cells specifically targeted to fight influenza ('Tcells'), in these groups. In the long term, the investigators hope that this will lead to designing new ways of improving the response to vaccines in HIVinfected people. As LAIV is given into each nostril, rather than an injection, the investigators also want to see if LAIV results in Tcells in the lung that are specifically targeted to fight influenza

Conditions

Acquired Immune Deficiency Syndrome Virus

Outcome Measures

Primary Outcomes (1)

• Differential gene expression at day 3 following administration of LAIV from baseline, via DNA microarrays.

  Do HIVinfected individuals have distinct differential early gene expression profiles following intranasal live attenuated influenza vaccine, when compared to age and sexmatched HIVnegative subjects, thus providing insights into the aberrant immunological response to live vaccines modulated by HIV infection?

  day 3

Study Arms (1)

Fluenz Tetra

EXPERIMENTAL

Live attenuated influenza vaccine- Fluenz tetra. Intra-nasal administration of 0.2ml (0.1ml in each nostril).

Biological: Live attenuated Vaccine- Fluenz Tretra

Interventions

Live attenuated Vaccine- Fluenz Tretra BIOLOGICAL

Intra-nasal administration of 0.2ml (0.1ml in each nostril).

Fluenz Tetra

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age18 - 49
• HIV1 infected
• On antiretroviral therapy
• CD4 count of \>200/mm3 (for at least 6 months, last available measurement within 3 months)
• Viral load undetectable (for at least 6 months, last available measurement within 3 months)
• Historyof having received at least one dose of trivalent inactivated influenza vaccine in the past
• Nonsmoker

You may not qualify if:

• Severe egg allergy
• Hypersensitivity to gentamicin
• Pregnant or breastfeeding
• Chronic lung disease (e.g. bronchiectasis)
• A history of severe asthma or current active wheezing
• Other cause for immunosuppression (e.g. malignancy) or immunosuppressive medication
• Hepatitis B or C coinfection (as defined by a detectable HBSAg or HCV RNA)
• Planned close contact with severely immunocompromised individuals in 2 weeks following LAIV (e.g bone marrow transplant recipients)
• Recipient of any other vaccination within the last 4 weeks
• Individuals who have had a febrile illness or other symptoms of acute infectious illness (respiratory, enteric or soft tissue) within the last 2 weeks.
• Individuals with a known and current history of anaemia or any symptoms (shortness of breath, chronic fatigue, chest pain or pallor) suggestive of possible anaemia or haemoglobin below the lower limit of sex adjusted normal range on a full blood count taken within the last 3 months.
• Current(active) participation in any clinical trial
• Inability to communicate in English or convey willingness to participate.

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead

Study Sites (1)

Sheffield Teaching Hospitals NHS Foundation trust

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 17, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: March 21, 2016

Record last verified: 2016-03

Locations

GB (1)