Investigation of Immunostimulatory Effects of IFN‐γ Cytokine and CD40 Ligand Costimulatory Molecule for Development of HIV‐1 Therapeutic Vaccine Candidate

Heidarnejad, Fatemeh; Bolhassani, Azam; Ajdary, Soheila; Milani, Alireza; Sadeghi, Seyed Amir

doi:10.1002/adbi.202300402

Cited by 3 publications

(1 citation statement)

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“…This is due, among other factors, to the production of CD40 receptor binding protein (CD40L) in CD4(+) T lymphocytes cocultured with EBV-infected B lymphocytes. CD40L can disfavor both the maintenance of EBV replication ( 51 ) and HIV replication ( 52 ) through the modulation of a consistent immune response. The fact that the HIV viral load was lower in the group with past infection than in the other groups may indicate that this process of immunological control occurs in the long term.…”

Section: Discussionmentioning

confidence: 99%

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region

Pereira,

dos Santos França,

Costa

et al. 2024

Front. Med.

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BackgroundEpstein–Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients.MethodsWe recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO.ResultsThe DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection.ConclusionOur results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

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Section: Discussionmentioning

confidence: 99%

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region

Pereira,

dos Santos França,

Costa

et al. 2024

Front. Med.

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Engineered ClearColi™-derived outer membrane vesicles as functional carriers for development of HIV-1 therapeutic vaccine candidate

Sadeghi,

Bolhassani,

Mohit

et al. 2024

Microbial Pathogenesis

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Heterologous DNA Prime/Protein Boost Immunization Targeting Nef-Tat Fusion Antigen Induces Potent T-cell Activity and in vitro Anti-SCR HIV-1 Effects

Sadeghi,

Bolhassani,

Mohit

et al. 2024

CHR

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Background: Heterologous combinations in vaccine design are an effective approach to promote T cell activity and antiviral effects. The goal of this study was to compare the homologous and heterologous regimens targeting the Nef-Tat fusion antigen to develop a human immunodeficiency virus-1 (HIV-1) therapeutic vaccine candidate. Methods: At first, the DNA and protein constructs harboring HIV-1 Nef and the first exon of Tat as linked form (pcDNA-nef-tat and Nef-Tat protein) were prepared in large scale and high purity. The generation of the Nef-Tat protein was performed in the E. coli expression system using an IPTG inducer. Then, we evaluated and compared immune responses of homologous DNA prime/ DNA boost, homologous protein prime/ protein boost, and heterologous DNA prime/protein boost regimens in BALB/c mice. Finally, the ability of mice splenocytes to secret cytokines after exposure to single-cycle replicable (SCR) HIV-1 was compared between immunized and control groups in vitro. Results: The nef-tat gene was successfully subcloned in eukaryotic pcDNA3.1 (-) and prokaryotic pET-24a (+) expression vectors. The recombinant Nef-Tat protein was generated in the E. coli Rosetta strain under optimized conditions as a clear band of ~ 35 kDa detected on SDS-PAGE. Moreover, transfection of pcDNA-nef-tat into HEK-293T cells was successfully performed using Lipofectamine 2000, as confirmed by western blotting. The immunization studies showed that heterologous DNA prime/protein boost regimen could significantly elicit the highest levels of Ig- G2a, IFN-γ, and Granzyme B in mice as compared to homologous DNA/DNA and protein/protein regimens. Moreover, the secretion of IFN-γ was higher in DNA/protein regimens than in DNA/DNA and protein/protein regimens after exposure of mice splenocytes to SCR HIV-1 in vitro. method: At first, the DNA and protein constructs harboring HIV-1 Nef and the first domain of Tat as linked form (pcDNA-nef-tat and Nef-Tat protein) were prepared in large scale and high purity. The generation of Nef-Tat protein was performed in E. coli expression system using IPTG inducer. Then, we evaluated and compared immune responses of homologous DNA prime/ DNA boost, homologous protein prime/ protein boost, and heterologous DNA prime/protein boost regimens in BALB/c mice. Finally, the ability of mice splenocytes to secret cytokines after exposure to HIV-1 single-cycle replicable (SCR) virions was compared between immunized and control groups in vitro. Conclusion: The chimeric HIV-1 Nef-Tat antigen was highly immunogenic, especially when applied in a heterologous prime/ boost regimen. This regimen could direct immune response toward cellular immunity (Th1 and CTL activity) and increase IFN-γ secretion after virus exposure.

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Investigation of Immunostimulatory Effects of IFN‐γ Cytokine and CD40 Ligand Costimulatory Molecule for Development of HIV‐1 Therapeutic Vaccine Candidate

Cited by 3 publications

References 58 publications

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region

Engineered ClearColi™-derived outer membrane vesicles as functional carriers for development of HIV-1 therapeutic vaccine candidate

Heterologous DNA Prime/Protein Boost Immunization Targeting Nef-Tat Fusion Antigen Induces Potent T-cell Activity and in vitro Anti-SCR HIV-1 Effects

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