scholarly journals Potent and Stable Attenuation of Live-HIV-1 by Gain of a Proteolysis-resistant Inhibitor of NF-κB (IκB-αS32/36A) and the Implications for Vaccine Development

1999 ◽  
Vol 274 (25) ◽  
pp. 17567-17572 ◽  
Author(s):  
Ileana Quinto ◽  
Massimo Mallardo ◽  
Francesca Baldassarre ◽  
Giuseppe Scala ◽  
George Englund ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Hiv 1

HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

2020 ◽  
Vol 28 ◽  
Author(s):  
Alireza Milani ◽  
Kazem Baesi ◽  
Elnaz Agi ◽  
Ghazal Marouf ◽  
Maryam Ahmadi ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Treated Group ◽  
Vaccine Antigen ◽  
Accessory Proteins ◽  
Serological Method ◽  
Th2 Immune Response ◽  
Untreated Individuals ◽  
Immunogenic Properties ◽  
Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

scholarly journals A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans

2004 ◽  
Vol 85 (4) ◽  
pp. 911-919 ◽  
Author(s):  
Matilu Mwau ◽  
Inese Cebere ◽  
Julian Sutton ◽  
Priscilla Chikoti ◽  
Nicola Winstone ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Vaccinia Virus ◽  
Mononuclear Cells ◽  
Vaccine Development ◽  
Cell Mediated Immunity ◽  
Phase I Clinical Trials ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Hiv 1

The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency virus (HIV) vaccines were evaluated on their own and in a prime–boost regimen in phase I clinical trials in healthy uninfected individuals in the United Kingdom. Given the current lack of approaches capable of inducing broad HIV-neutralizing antibodies, the pTHr.HIVA DNA and MVA.HIVA vaccines focus solely on the induction of cell-mediated immunity. The vaccines expressed a common immunogen, HIVA, which consists of consensus HIV-1 clade A Gag p24/p17 proteins fused to a string of clade A-derived epitopes recognized by cytotoxic T lymphocytes (CTLs). Volunteers' fresh peripheral blood mononuclear cells were tested for HIV-specific responses in a validated gamma interferon enzyme-linked immunospot (ELISPOT) assay using four overlapping peptide pools across the Gag domain and three pools of known CTL epitopes present in all of the HIVA protein. Both the DNA and the MVA vaccines alone and in a DNA prime–MVA boost combination were safe and induced HIV-specific responses in 14 out of 18, seven out of eight and eight out of nine volunteers, respectively. These results are very encouraging and justify further vaccine development.

scholarly journals Construction of A Preliminary Three-Dimensional Structure Simian betaretrovirus Serotype-2 (SRV-2) Reverse Transcriptase Isolated from Indonesian Cynomolgus Monkey

2020 ◽  
Vol 31 (3) ◽  
pp. 47-61
Author(s):  
Uus Saepuloh ◽  
Diah Iskandriati ◽  
Joko Pamungkas ◽  
Dedy Duryadi Solihin ◽  
Sela Septima Mariya ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Cynomolgus Monkey ◽  
Tertiary Structure ◽  
Vaccine Development ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Nucleotide Position ◽  
Structure Model ◽  
Three Dimensional Structure ◽  
Hiv 1

Simian betaretrovirus serotype-2 (SRV-2) is an important pathogenic agent in Asian macaques. It is a potential confounding variable in biomedical research. SRV-2 also provides a valuable viral model compared to other retroviruses which can be used for understanding many aspects of retroviral-host interactions and immunosuppression, infection mechanism, retroviral structure, antiretroviral and vaccine development. In this study, we isolated the gene encoding reverse transcriptase enzyme (RT) of SRV-2 that infected Indonesian cynomolgus monkey (Mf ET1006) and predicted the three dimensional structure model using the iterative threading assembly refinement (I-TASSER) computational programme. This SRV-2 RT Mf ET1006 consisted of 547 amino acids at nucleotide position 3284–4925 of whole genome SRV-2. The polymerase active site located in the finger/palm subdomain characterised by three conserved catalytic aspartates (Asp90, Asp165, Asp166), and has a highly conserved YMDD motif as Tyr163, Met164, Asp165 and Asp166. We estimated that this SRV-2 RT Mf ET1006 structure has the accuracy of template modelling score (TM-score 0.90 ± 0.06) and root mean square deviation (RMSD) 4.7 ± 3.1Å, indicating that this model can be trusted and the accuracy can be seen from the appearance of protein folding in tertiary structure. The superpositionings between SRV-2 RT Mf ET1006 and Human Immunodeficiency Virus-1 (HIV-1) RT were performed to predict the structural in details and to optimise the best fits for illustrations. This SRV-2 RT Mf ET1006 structure model has the highest homology to HIV-1 RT (2B6A.pdb) with estimated accuracy at TM-score 0.911, RMSD 1.85 Å, and coverage of 0.953. This preliminary study of SRV-2 RT Mf ET1006 structure modelling is intriguing and provide some information to explore the molecular characteristic and biochemical mechanism of this enzyme.

scholarly journals 2838. Safety and Immunogenicity of a gp120-CD4 Chimeric Subunit Vaccine: A Phase 1a Randomized Controlled Trial

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S65-S66
Author(s):  
Joel V Chua ◽  
Charles Davis ◽  
Amy Nelson ◽  
Ka Wing J Lam ◽  
Lydiah Mutumbi ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Vaccine Development ◽  
Controlled Trial ◽  
Chimeric Protein ◽  
Controlled Study ◽  
Control Group ◽  
Single Chain ◽  
Double Blind ◽  
Humoral Responses ◽  
Hiv 1

Abstract Background A primary challenge for HIV vaccine development is to raise antiviral antibodies capable of recognizing highly variable viral antigens. The full-length single chain (FLSC) gp120-CD4 chimeric protein was designed to present a highly conserved CD4-induced HIV-1 envelope structure that evokes cross-reactive humoral responses (Figure 1). IHV01 is an FLSC subunit vaccine formulated in alum adjuvant. The safety and immunogenicity of IHV01 was evaluated in this first-in-human phase 1a trial. Methods This randomized, double-blind placebo-controlled study involved three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Eligible participants were HIV-1 uninfected healthy volunteers aged 18 to 45 years. Participants in each cohort were block randomized in groups of four in a 3:1 ratio to receive either vaccine or placebo. Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. Crossreactive antibody binding titers against diverse HIV envelopes and antigens and specific CD4i epitopes on gp120 were assessed. Results Sixty-five volunteers were enrolled—49 vaccine and 16 placebo. Majority (81%) of vaccinations with IHV01 produced no localized or systemic reactions; no different from the control group. The overall incidence of adverse events (AEs) was not significantly different between groups. Majority (89%) of vaccine-related AEs were mild in severity. The most common vaccine-related AEs were injection site pain (31%), pruritus (10%), and headache (10%). There were no vaccine-related serious AE, discontinuation due to AE, or intercurrent HIV infection. By the final vaccination, all subjects in all cohorts had developed antibodies against IHV01; all placebo recipients were negative. The antibodies induced by IHV01 reacted with envelope antigens from diverse HIV-1 strains (Figure 2). Conclusion IHV01 vaccine was safe, well tolerated, and immunogenic in all doses tested. The vaccine raised broadly reactive humoral responses against multiple gp120 domains, transition state structures, and CD4i epitopes. Disclosures All Authors: No reported Disclosures.

scholarly journals B-cell–lineage immunogen design in vaccine development with HIV-1 as a case study

2012 ◽  
Vol 30 (5) ◽  
pp. 423-433 ◽  
Author(s):  
Barton F Haynes ◽  
Garnett Kelsoe ◽  
Stephen C Harrison ◽  
Thomas B Kepler
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Cell Lineage ◽  
Immunogen Design ◽  
Hiv 1

scholarly journals Potential of recombinant Mycobacterium paragordonae expressing HIV-1 Gag as a prime vaccine for HIV-1 infection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Byoung-Jun Kim ◽  
Bo-Ram Kim ◽  
Yoon-Hoh Kook ◽  
Bum-Joon Kim
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Antibody Production ◽  
Vaccine Development ◽  
Cytotoxic T Lymphocyte ◽  
Mycobacterial Infection ◽  
Temperature Sensitive ◽  
T Lymphocyte Proliferation ◽  
Antigen Presenting ◽  
Hiv 1

Abstract Recombinant Mycobacterium strains such as recombinant BCG (rBCG) have received considerable attention for the HIV-1 vaccine development. Recently, we described a temperature-sensitive Mycobacterium paragordonae (Mpg) strain as a novel live tuberculosis vaccine that is safer and showed an enhanced protective effect against mycobacterial infection compared to BCG. We studied the possibility of developing a vaccine against HIV-1 infection using rMpg strain expressing the p24 antigen (rMpg-p24). We observed that rMpg-p24 can induce an increased p24 expression in infected antigen presenting cells (APCs) compared to rBCG-p24. We also observed that rMpg-p24 can induce enhanced p24 specific immune responses in vaccinated mice as evidenced by increased p24-specific T lymphocyte proliferation, gamma interferon induction, antibody production and cytotoxic T lymphocyte (CTL) responses. Furthermore, an rMpg-p24 prime and plasmid DNA boost showed an increased CTL response and antibody production compared to rBCG or rMpg alone. In summary, our study indicates that a live rMpg-p24 strain induced enhanced immune responses against HIV-1 Gag in vaccinated mice. Thus, rMpg-p24 may have potential as a preventive prime vaccine in a heterologous prime-boost regimen for HIV-1 infection.

scholarly journals Broadly neutralizing antibodies and vaccine design against HIV-1 infection

2019 ◽  
Vol 14 (1) ◽  
pp. 30-42 ◽  
Author(s):  
Qian Wang ◽  
Linqi Zhang
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vaccine Design ◽  
Therapeutic Interventions ◽  
Type I ◽  
Broadly Neutralizing Antibodies ◽  
Dynamic Studies ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Remarkable Progress

AbstractRemarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I (HIV-1) through antiretroviral therapy. However, vaccine development has remained challenging. Recent discoveries in broadly neutralizing monoclonal antibodies (bNAbs) has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response. Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein (Env) during infection. Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development.

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