title: A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV).
abstract: BACKGROUND
  The Capripoxvirus, Lumpy skin disease virus (LSDV) has a restricted host-range and is being investigated as a novel HIV-1 vaccine vector. LSDV does not complete its replication cycle in non-ruminant hosts.
  
  
  METHODS
  The safety of LSDV was tested at doses of 104 and 106 plaque forming units in two strains of immunocompromised mice, namely RAG mice and CD4 T cell knockout mice. LSDV expressing HIV-1 subtype C Gag, reverse transcriptase (RT), Tat and Nef as a polyprotein (Grttn), (rLSDV-grttn), was constructed. The immunogenicity of rLSDV-grttn was tested in homologous prime-boost regimens as well as heterologous prime-boost regimes in combination with a DNA vaccine (pVRC-grttn) or modified vaccinia Ankara vaccine (rMVA-grttn) both expressing Grttn.
  
  
  RESULTS
  Safety was demonstrated in two strains of immunocompromised mice.In the immunogenicity experiments mice developed high magnitudes of HIV-specific cells producing IFN-gamma and IL-2. A comparison of rLSDV-grttn and rMVA-grttn to boost a DNA vaccine (pVRC-grttn) indicated a DNA prime and rLSDV-grttn boost induced a 2 fold (p < 0.01) lower cumulative frequency of Gag- and RT-specific IFN-γ CD8 and CD4 cells than a boost with rMVA-grttn. However, the HIV-specific cells induced by the DNA vaccine prime rLSDV-grttn boost produced greater than 3 fold (p < 0.01) more IFN- gamma than the HIV-specific cells induced by the DNA vaccine prime rMVA-grttn boost. A boost of HIV-specific CD4 cells producing IL-2 was only achieved with the DNA vaccine prime and rLSDV-grttn boost. Heterologous prime-boost combinations of rLSDV-grttn and rMVA-grttn induced similar cumulative frequencies of IFN- gamma producing Gag- and RT-specific CD8 and CD4 cells. A significant difference (p < 0.01) between the regimens was the higher capacity (2.1 fold) of Gag-and RT-specific CD4 cells to produce IFN-γ with a rMVA-grttn prime - rLSDV-grttn boost. This regimen also induced a 1.5 fold higher (p < 0.05) frequency of Gag- and RT-specific CD4 cells producing IL-2.
  
  
  CONCLUSIONS
  LSDV was demonstrated to be non-pathogenic in immunocompromised mice. The rLSDV-grttn vaccine was immunogenic in mice particularly in prime-boost regimens. The data suggests that this novel vaccine may be useful for enhancing, in particular, HIV-specific CD4 IFN- gamma and IL-2 responses induced by a priming vaccine.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, UCT, Cape Town, South Africa.
authors.forename: Yen-Ju
authors.initials: YJ
authors.lastname: Shen
authors.forename: Enid
authors.initials: E
authors.lastname: Shephard
authors.forename: Nicola
authors.initials: N
authors.lastname: Douglass
authors.forename: Nicolette
authors.initials: N
authors.lastname: Johnston
authors.forename: Craig
authors.initials: C
authors.lastname: Adams
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D003673:Defective Viruses / Q000235:genetics / Q000472:pathogenicity*; D004337:Drug Carriers; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D016867:Immunocompromised Host; D008167:Lumpy skin disease virus / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D018345:Mice, Knockout; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D004337:Drug Carriers; D014614:Vaccines, Synthetic