Immunogenicity of Inactivated Swine H1N1 Vaccine In HIV Infected Children - The Miami Cohort Study
Condition: HIV
Study type: Observational

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Perinatally Infected Children
      
Biospecimen description: 
      Frozen PBMC for future experiments as per results.
    
Keywords: H1N1; HIV; Immunogenecity