title: Safety and immunogenicity of DNA and MVA HIV-1 subtype C vaccine prime-boost regimens: a phase I randomised Trial in HIV-uninfected Indian volunteers.
abstract: METHODS
  A randomized, double-blind, placebo controlled phase I trial.
  
  
  METHODS
  The trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of prime-boost vaccination regimens with either 2 doses of ADVAX, a DNA vaccine containing Chinese HIV-1 subtype C env gp160, gag, pol and nef/tat genes, as a prime and 2 doses of TBC-M4, a recombinant MVA encoding Indian HIV-1 subtype C env gp160, gag, RT, rev, tat, and nef genes, as a boost in Group A or 3 doses of TBC-M4 alone in Group B participants. Out of 16 participants in each group, 12 received vaccine candidates and 4 received placebos.
  
  
  RESULTS
  Both vaccine regimens were found to be generally safe and well tolerated. The breadth of anti-HIV binding antibodies and the titres of anti-HIV neutralizing antibodies were significantly higher (p<0.05) in Group B volunteers at 14 days post last vaccination. Neutralizing antibodies were detected mainly against Tier-1 subtype B and C viruses. HIV-specific IFN-γ ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN-γ ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1(st) and 2(nd) MVA doses as compared to the responses in group B volunteers. However, the priming effect was short lasting leading to no difference in the frequency, breadth and magnitude of IFN-γELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination.
  
  
  CONCLUSIONS
  Although DNA priming resulted in enhancement of immune responses after 1(st) MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting.
  
  
  BACKGROUND
  Clinical Trial Registry CTRI/2009/091/000051.
authors: National Institute of Epidemiology, Chennai, India. sanjaymehendale@icmr.org.in
authors: Sanjay
authors: S
authors: Mehendale
authors: Madhuri
authors: M
authors: Thakar
authors: Seema
authors: S
authors: Sahay
authors: Makesh
authors: M
authors: Kumar
authors: Ashwini
authors: A
authors: Shete
authors: Pattabiraman
authors: P
authors: Sathyamurthi
authors: Amita
authors: A
authors: Verma
authors: Swarali
authors: S
authors: Kurle
authors: Aparna
authors: A
authors: Shrotri
authors: Jill
authors: J
authors: Gilmour
authors: Rajat
authors: R
authors: Goyal
authors: Len
authors: L
authors: Dally
authors: Eddy
authors: E
authors: Sayeed
authors: Devika
authors: D
authors: Zachariah
authors: James
authors: J
authors: Ackland
authors: Sonali
authors: S
authors: Kochhar
authors: Josephine H
authors: JH
authors: Cox
authors: Jean-Louis
authors: JL
authors: Excler
authors: Vasanthapuram
authors: V
authors: Kumaraswami
authors: Ramesh
authors: R
authors: Paranjape
authors: Vadakkuppatu Devasenapathi
authors: VD
authors: Ramanathan
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology; D000328:Adult; D057134:Antibodies, Neutralizing; D004311:Double-Blind Method; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007194:India; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000276:immunology; D014615:Vaccinia / Q000517:prevention & control; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; C560489:MVA vaccine; D019444:Vaccines, DNA; D014765:Viral Vaccines