Slide 1 HIV Vaccine Trials Network Science Tutorial An Overview of “Studies in Response to by pengxiang


									Science Tutorial

An Overview of
“Studies in Response to the Step Study”
Tuesday, November 17, 8:30 to 9:50 AM

         Stephen De Rosa
         HVTN Laboratory Program
General comments about plenary

 Studies examining antibody responses
  (immune responses broadly
  categorized between T cells and
  antibodies). Antibody often
  abbreviated Ab.
 Responses induced by the vaccine
 Not to be confused with neutralizing
  antibodies to Ad5 measured at baseline
  (abbreviated nAb)
 Adenovirus serotype 5 (Ad5)

 Adenovirus serotype 5 (Ad5) is the viral
  vector used in Step – engineered to
  encode for HIV proteins
 Ad5 is a virus that can cause a “cold”,
  some people have been “naturally”
  infected with Ad5
 Initial results from Step study indicated
  increased risk of HIV infection only in
  vaccine recipients previously Ad5-
  infected (have neutralizing Ad5 Ab)
 Responses to Ad5 and risk of HIV
 infection in Step

 General question – what is the
  immunological mechanism for this
  increased infection risk?
 Is it related to the immune response to
  the Ad5 vector?
 Antibody and T cell responses to Ad5
  vector measured.
 Not to be confused with antibody and T
  cell responses to HIV proteins encoded
  by Ad vector.
 Summary of “Ad5 Seroprevalence in
 the Step study” by Dan Barouch

 Hypothesis is that vaccine-induced
  stimulation of prior T cell responses to
  Ad5 increased “target” cells for HIV
  infection, in blood or at mucosa
 Four studies summarized
 Overall, Ad5 T cell responses do not
  explain enhanced HIV acquisition in Step
 Ad cross-reactive responses (Ab or T cell)
  not correlated with HIV infection
 Summary of “Analysis of the specificity of
 neutralizing antibodies to Ad5 and
 correlation with vaccine-induced immunity
 and infection in the Step study: Interim
 report” by Cheng Cheng
 Specificity refers to the part of the Ad
  virus, fiber vs. capsid (the neutralization
 Responses to fiber and/or capsid differ
  depending on natural infection vs. Ad5
 Lower nAb responses to fiber in cases vs.
  non-cases (p=0.06)
 Biological significance to be determined
  Summary of “HIV-1 specific IgG
  isotype serology in infected
  volunteers from the Step study” by
  John Moore
 Hypothesis: pre-existing immunity to Ad5
  may alter how the Ad5 vaccine is
  processed and may alter the type of
  antibody response induced
 Examined antibody subtypes, not just
  total antibody to HIV Env protein
 No differences found vaccine vs. placebo
 Summary of “Does Ad5 Gag-Pol-
 Nef vaccination elicit antibodies
 that enhance HIV infection?” by
 Donald Forthal
 For the HIV virus, this potentially harmful
  effect has only been examined in vitro.
 Hypothesized to be mainly for Env
  antibodies (on surface of virus), but Env
  not included in Step vaccine.
 But Nef may be expressed on infected
  cells – therefore can examine in Step
 Step samples not analyzed yet; no effect
  found in Merck phase I study samples
 Conclusion overall

 Two years following the termination of
  the Step trial, no evidence for a biologic
  reason for pre-vaccination Ad5 immunity
  increasing risk of HIV acquisition

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