title: Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous prime-boost HIV-1 vaccine on insert-specific immune responses.
abstract: BACKGROUND
  The impact of anti-vector immunity on the elicitation of insert-specific immune responses is important to understand in vaccine development. HVTN 055 was a 150 person phase I randomized, controlled HIV vaccine trial of recombinant modified vaccinia Ankara (rMVA) and fowlpox (rFPV) with matched HIV-1 inserts which demonstrated increased CD8+ T-cell immune responses in the heterologous vaccine group. The controls used in this study were the empty vectors (MVA and FPV).
  
  
  METHODS
  Anti-MVA and anti-vaccinia neutralizing antibodies (NAbs) were measured and compared with cellular and humoral HIV-1-specific immune responses.
  
  
  RESULTS
  Elicitation of anti-vector responses increased with increasing dose of MVA and up to 2 administrations. Further inoculations of MVA (up to 5) did not increase the magnitude of the anti-MVA response but did delay the anti-vector NAb titre decay. There was no evidence that the insert impaired the anti-vector response, nor that anti-vector immunity attenuated the insert-specific responses.
  
  
  CONCLUSIONS
  Two doses of MVA may be ideal for the elicitation of orthopoxvirus immune responses with further doses maintaining increased titres against the vector. We found no evidence that eliciting HIV insert- or MVA vector-specific immune responses interfered with elicitation of immune responses to the other.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, United States. srwalsh@bidmc.harvard.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Grandpre
authors.forename: Cherie
authors.initials: C
authors.lastname: Charbonneau
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Yanosick
authors.forename: Barbara
authors.initials: B
authors.lastname: Metch
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005587:Fowlpox virus / Q000276:immunology; D006801:Humans; D018155:Orthopoxvirus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing