HIV-1;
p24-Nef;
DNA;
protein prime-boost vaccine;
therapeutic;
in silico;
vaccine;
IMMUNE-RESPONSES;
NEF ANTIGEN;
STRATEGY;
D O I:
10.2174/1567201818666210101113601
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Background: There have been massive efforts on vaccine development against HIV-1 since its discovery. Various approaches have been taken to attention, including rational vaccine design, optimized delivery systems and heterologous regimen to eradicate the virus. DNA vaccines fundamentally induce host immune responses by genetically engineered plasmids encoding antigens and expressed in vivo without the need of the specific delivery system. Therefore, long-term endogenous antigen expression could be possible. Objective: In this study, we aimed at evaluation and comparison of DNA and protein vaccine based on two forms of full and truncated HIV-1 p24-nef antigens by in silico design in BLALB/c. Methods: The recombinant pcDNA3.1 harboring two sets of HIV-1 p24 and nef genes in truncated and full forms were generated and applied to immunize BALB/c along with the corresponding proteins via three different DNA/DNA, DNA/protein and protein/protein regimens. Results: The results showed that the applied regimens could elicit strong immune responses in comparison with controls and the prim-boost DNA/protein regimen reached the highest immune induction (p < 0.05). Moreover, prime-boost approach was assessed more successfully in a qualitatively broad Th1 response induction. The truncated form of the antigens, p24(80-231 aa)-AAY-Nef (120-150), was evaluated more immunogenic in agreement with the in silico investigation. Conclusion: The truncated form of p24-Nef was evaluated highly immunogenic specially when applied in prim-boost DNA/Protein regimen and could be investigated in other delivery systems and a proper animal model to achieve a therapeutic vaccine candidate against HIV-1.
机构:
Hosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Hosp Univ Vall dHebron, Vall dHebron Res Inst, Barcelona 08035, Catalonia, SpainHosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Kilpelainen, Athina
Saubi, Narcis
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Hosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Hosp Univ Vall dHebron, Vall dHebron Res Inst, Barcelona 08035, Catalonia, SpainHosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Saubi, Narcis
Guitart, Nuria
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Hosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, SpainHosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Guitart, Nuria
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Olvera, Alex
Hanke, Tomas
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机构:
Univ Oxford, Jenner Inst, Nuffield Dept Med, Oxford OX3 7DQ, England
Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto 8600811, JapanHosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Hanke, Tomas
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Brander, Christian
Joseph, Joan
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Hosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain
Hosp Univ Vall dHebron, Vall dHebron Res Inst, Barcelona 08035, Catalonia, SpainHosp Clin IDIBAPS, Catalan Ctr HIV Vaccine Res & Dev, AIDS Res Unit, Infect Dis Dept, Barcelona 08036, Catalonia, Spain