NHVREI Year Planning HVTN Communications plans

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					                      HVTN 069


       A phase IB trial to compare safety, tolerability, and
 immunogenicity of HIV-1 adenoviral vector boost administered
intramuscularly, intradermally or subcutaneously after an HIV-1
  DNA plasmid vaccine prime administered intramuscularly to
 healthy adenovirus type 5 seropositive HIV-1-uninfected adults



           Chair: Beryl Koblin, New York Blood Center
              Co-chair: Martin Casapia, IMPACTA
Rationale for trial
 Vaccines with demonstrated immunogenicity
 Can we improve on this?
   Route of administration
 SC and ID routes and antigen-presenting
  cells in the skin
 Previous experience:
   ID > IM: influenza, hepatitis B
   SC comparable to IM examples: anthrax, varicella,
    meningococcal polysaccharide
   Frequency of side effects higher but transient
Products
 VRC 4-plasmid DNA vaccine
   VRC-HIVDNA009-00-VP
   Clade B HIV-1 Gag/Pol/Nef, Env from
    Clades A, B, C


 VRC Ad5 vector vaccine
   VRC-HIVADV014-00-VP
   Clade B HIV-1 Gag/Pol, Env from
    Clades A, B, C
Primary objectives
 Safety of the DNA prime and Ad5
  boost given either IM, ID or SC.
 To compare ID vs. IM and SC vs. IM
  to determine if either ID or SC is
  superior to IM in eliciting vaccine-
  induced HIV-specific T cell responses
   Magnitude of IFN-g ELISPOT responses at
    4 weeks after the Ad5 boost
Secondary objectives
 To compare ID vs. IM and SC vs. IM
  in response rate and magnitude of
  ICS responses at 4 weeks after Ad5
  boost
 Evaluate HIV specific binding
  antibody responses assessed by
  ELISA at 4 weeks after Ad5 boost
 Describe social impact of participation
 Schema
                       Vaccination schedule in months (days)
                                    Prime                 Boost
Study arm     N         0 (0)       1 (28)     2 (56)    6 (168)
                       4 mg         4 mg        4 mg     1010 PU
 Group 1     30         DNA         DNA         DNA      Ad5 IM

                       4 mg        4 mg        4 mg     1010 PU
 Group 2     30        DNA         DNA         DNA      Ad5 ID

                       4 mg        4 mg        4 mg     1010 PU
 Group 3     30        DNA         DNA         DNA      Ad5 SC
Total        90

Eligibility: Ad5 titer > 1:12
Sites
   Birmingham, AL
   Boston, MA
   Iquitos, Peru
   New York, NY
   Seattle, WA
Demographics (N=90)
      Characteristic          N     %
      Female                  37   41.1
      Race/ethnicity
        White                 36   40.0
        Hispanic              29   32.2
        Black                 16   17.8
        Multiracial           4    4.4
        Asian                 4    4.4
        Native American       1    1.1

      Median age = 27 years
Doses and retention (N=90)
       Characteristic      N     %

       Doses received

       1                   2    2.2

       2                   4    4.4

       3                   23   25.6

       4                   61   67.8
       Retention at last
       visit               85   94.4
 Local reactogenicity
       Pain and/or tenderness p= 0.91                        Induration p= 0.04
100%                                     100%



80%                                      80%



60%                                      60%



40%                                      40%



20%                                      20%




 0%                                       0%
         IM          ID          SC                    IM             ID           SC

       None   Mild   Moderate   Severe          None        <25 cm2   25-81 cm2   >81 cm2
Systemic reactogenicity
 No differences by treatment arm for:
     Malaise/fatigue
     Myalgia
     Headache
     Nausea
     Vomiting
     Chills
     Arthralgia
     Temperature
ELISpot results –
Overall response rate by treatment


     Treatment   2 weeks post    4 weeks post
     arm            VAC 3           VAC 4
     IM          8/17 (47.1%)    7/15 (46.7%)
     ID          10/21 (47.6%)   6/18 (33.3)
     SC          6/19 (31.6%)    8/18 (44.4)
      HVTN 069 IFN-γ ELISpot Responses by gene
      and treatment (Global PTE peptides)
                                                              2 Weeks post-VAC 3
                             2/20        8/17    1/17                  10/21                      6/19         2/19
IFN-γ SFC/106 PBMC




                            Day 0        Env     Gag    Nef      Pol    Env     Gag    Nef      Pol      Env    Gag    Nef      Pol

                                                DNA + Ad5 (IM)                 DNA + Ad5 (ID)                  DNA + Ad5 (SC)
                     Positive response          Negative response
            HVTN 069 IFN-γ ELISpot Responses by gene
            and treatment (Global PTE peptides)
                                                                   4 Weeks post-VAC 4
                             2/20   6/15       2/15          4/15      6/18                          8/18   2/18          3/18
IFN-γ SFC/106 PBMC




                            Day 0        Env    Gag    Nef      Pol    Env     Gag    Nef      Pol   Env     Gag    Nef      Pol

                                               DNA + Ad5 (IM)                 DNA + Ad5 (ID)                DNA + Ad5 (SC)
                     Positive response         Negative response
ELISpot results –
Overall response rate by Ad5 and treatment

               2 weeks post VAC 3   4 weeks post VAC 4


   Treatment    Ad5        Ad5       Ad5       Ad5
   arm         12-500      >500     12-500     >500
                 3/5        5/12      3/5       4/10
   IM          (60.0%)    (41.7%)   (60.0%)   (40.0%)
                 2/5        8/16      1/5       5/13
   ID          (40.0%)    (50.0%)   (20.0%)   (38.5%)
                 4/11       2/8       3/9       5/9
   SC          (36.4%)    (25.0%)   (33.3%)   (55.6%)
Summary
 DNA and Ad5 vaccines well tolerated
   Higher % with induration with ID and SC
 No differences in immunogenicity by
  arm
 Overall response rates lower than
  expected
   All Ad5 positive
   Same lot as HVTN 204
Protocol Team
   Beryl Koblin and Martin            Barney Graham, Mary
    Casapia, Chair and Co-chair         Enama, Vaccine Research
   Cecilia Morgan, Protocol            Center, NIH
    Team Leader                        Krista Goodman, Clinic
   Li Qin, Maggie Wang, Liza           Coordinator
    Noonan, Statisticians              Columbus Gaskins, CAB
   Chuen-Yen Lau, Medical
    Officer                            DAIDS, NIAID, NIH
   Sites                              HVTN Laboratory Operations
       Birmingham: Paul Goepfert      HVTN Core
       Boston: Lindsey Baden
                                       SCHARP
       Iquitos: Martin Casapia
       NYC: Scott Hammer, Magda
        Sobieszczyk                    Clinic coordinators and staff
       Seattle: Julie McElrath
                                       Study participants!!

				
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