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: Yen-Ju Shen, Enid Shephard, Nicola Douglass, Nicolette Johnston, Craig Adams, Carolyn Williamson, Anna-Lise Williamson
• Journal: Virology journal (Virol J) Vol. 8 Pg. 265 (May 30 2011) ISSN: 1743-422X [Electronic] England
• PMID: 21624130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• Antigens, Viral
• Drug Carriers
• Vaccines, Synthetic

Topics

• AIDS Vaccines (adverse effects, genetics, immunology)
• Animals
• Antigens, Viral (genetics, immunology)
• Defective Viruses (genetics, pathogenicity)
• Drug Carriers
• Genetic Vectors
• HIV Infections (immunology, prevention & control)
• HIV-1 (genetics, immunology)
• Immunization, Secondary (methods)
• Immunocompromised Host
• Lumpy skin disease virus (genetics, pathogenicity)
• Mice
• Mice, Knockout
• Vaccination (methods)
• Vaccines, Synthetic (adverse effects, genetics, immunology)