Clinical trial NCT02031874: Immunogenicity of Inactivated Swine H1N1 Vaccine In HIV Infected Children - The Miami Cohort Study
Official title: Immunogenicity of Inactivated Swine H1N1 Vaccine In HIV Infected Children - The Miami Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Keywords: H1N1
HIV
Immunogenecity
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Vaccine and Gene Therapy Institute, Florida
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2014-01-09
Enrollment: 33
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Perinatally Infected Children

Brief summary: Immunosuppressed patients are at increased risk for complications of influenza infection, including secondary pneumonia and are recommended for annual influenza vaccination. Thus, the appearance of a novel subtype of influenza A virus designated as 2009 swine H1N1 virus has added an extra layer of complexity in the immunization regimen in this population. In general, susceptibility to swine H1N1 infection among young population is higher as young adults and children completely lack protective titers. According to the Center for Disease Control (CDC), 70 percent of people hospitalized with H1N1 have been "high risk" cases, including persons 65 years of age or older, or people with compromised immune systems as observed during HIV infection. This has prompted CDC to include HIV infected children to be one of the five groups to be vaccinated with the new H1N1 vaccine (National Center for Immunization). Currently no information exists about the nature of the immune response to the vaccine against H1N1 swine-origin influenza virus (S-OIV) in HIV infected children. It is unknown whether HIV impairs the immunogenicity of the vaccine predisposing this population to infection with S-OIV. Thus, a pilot proposal is being undertaken to study the mechanism of H1N1 vaccine protection in HIV infected children, by investigating the correlation of infection status with seroresponse, duration of response and development of influenza-like illness following vaccine. Additionally we will establish whether we can identify immune signatures by characteristic gene expression patterns correlating with the vaccine immunogenicity that can be predictive of efficacy for "good" and "suboptimal" vaccination regimen. Data generated will be used to initiate a comprehensive study on the immunogenicity of the influenza vaccines in HIV-infected children and youth, which is critically important to address the health care needs of this vulnerable population.

Detailed description: Patients will be recruited from HIV-1 outpatient clinic at the time the novel H1N1 vaccine becomes available. Demographic data will be collected after enrollment including HIV-1 viral load (VL) and CD4 count from last visit, antiretroviral therapy, gender and age. Patients will be asked to document adverse reactions observed during this study such as tenderness, pain, redness, and swelling at the injection site as well as systemic adverse reactions such as headache, malaise, and muscle aches. A subject will be withdrawn from the study if a serious adverse reaction occurs such as allergic reaction to a vaccine component or development with a progressive neurological disorder without definitive diagnosis. Statistical analysis will be performed after the viral load and CD4 counts are resulted from the day 30. The microneutralization assays and the titers will be analyzed post day 7 and 37. If the cohort does not seem to generate adequate responses, the study will be discontinued and no further samples collected.

Vaccination:

Since immunocompromised persons may have a diminished immune response to Influenza A (H1N1) 2009 Monovalent Vaccine, a higher antigen load will be used for this study as recommended by the National Center for Immunization and Respiratory Diseases and Centers for Disease Control and Prevention. All of the patients will be given a 0.5 ml intramuscular doses of A/California/7/2009 H1N1 strain inactivated vaccine in the deltoid muscle; all patients will receive a second dose after 4 weeks. Each vaccine dose will contain 15 µg each of H1N1 monovalent antigen. Patients under the age of 9 will receive the second vaccine as standard of care, while patients 9 and older will receive a second dose as part of this study.

Study Design:

This is a pilot study designed to recruit 72 patients with CD4 counts of ≥200. Patients will be enrolled on a first come first serve basis and will attempt to reach equal numbers in gender. A dose (15 µg) of the vaccine will be administered at day 0 and 30. Blood samples will be collected as in Table 1 (see Below). At each visit, the total maximum amount collected will be 17.5 ml divided in three individual samples: The first sample will be 5 ml for serum separation used in the detection of Hemagglutination inhibition (HI) titers and micro-neutralization (MN) assays. The second sample will be 10 ml processed for viral load, CD4 counts and ELISPOT functional B cell assays. The third sample will be 2.5 ml collected in a Paxgene RNA tube for future microarray testing. Based on the HI titer and MN responses obtained, the patients will be classified into three distinct subgroups: (a) high responders with ≥ 4 fold titer increases compared to baseline, (b) moderate responders with ≥ 2 and \< 4 fold increases and (c) low responders with \< 2 fold increases. From these subgroups, up to 25 complete patient's samples from the high and low responders will be selected for microarray studies. The microarray will compare readings from all visits. These preliminary data will serve the basis for future humoral and innate immunity gene activation.

Hemagglutination inhibition (HI) and microneutralization (MN) assays will be performed on blood samples collected as described in Table 1. Two individual samples will be collected in each visit, one will be used for serum separation used in the detection of HI titers and the second sample for viral load, CD4 counts, ELISPOT and Microarray testing. Based on the HI and MN titer responses obtained, the patients will be classified into three distinct subgroups: (a) high responders with ≥ 4 fold titer increases compared to baseline, (b) moderate responders with ≥ 2 and \< 4 fold increases and (c) low responders with \< 2 fold increases. From these subgroups, up to 25 complete samples from the high, moderate and low responders will be selected for viral load and microarray studies.

Eligibility criteria: Inclusion Criteria:

* Individuals must have a positive ELISA with confirm with a western blot after 18 months of age or a positive DNA or RNA PCR

Exclusion Criteria:

* Patients with hypersensitivity to eggs or chicken protein, neomycin, or polymyxin, or life-threatening reaction to previous influenza vaccination will be excluded. Pregnant individuals will be excluded from the study at this time. Patients with a previous episode of Guillain-Barré Syndrome (GBS) in relation to a previous influenza vaccination, will also be excluded. Allergic reactions, including anaphylactic shock

Primary outcomes:
measure: Determine immunogenecity to vaccine
timeFrame: 1 month
Secondary outcomes:
measure: Measure Antibody Response
timeFrame: 6 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Ivan A Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
References: