The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of SAR441236, a tri-specific broadly neutralizing antibody against the human immunodeficiency virus (HIV).

Start Date20 May 2019

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+2]

NCT00187148 / CompletedPhase 1IIT

Evaluation of the Tolerability and Safety of a Recombinant HIV-1 Multi-Envelope DNA Plasmid Vaccine (EnvDNA) in Healthy Adults

This protocol will evaluate the safety and tolerability of the vaccine EnvDNA in healthy adults. DNA-based vaccines are being studied for the prevention of human immunodeficiency virus (HIV), malaria and hepatitis. DNA vaccines have been well tolerated in human studies to date. The vaccine that will be tested in this study was made from the information that the virus uses to make a small part of the HIV. This small part is called the envelope or coating around the virus. We hope the body will make an immune response against the HIV envelope coat. Our potential HIV DNA envelope vaccine is called EnvDNA.

Start Date01 Feb 2005

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

[+1]

NCT00187044 / CompletedPhase 1IIT

Evaluation of the Safety of a Polyvalent Vaccinia Virus-HIV-1 Envelope Recombinant Vaccine (PolyEnv1) in Healthy Adults

This is a research study to evaluate the safety of a vaccine to protect people from HIV infection. Human Immunodeficiency Virus (HIV) is the cause of AIDS (Acquired Immune Deficiency Syndrome). AIDS is one of the most serious viral infections of our time. It is believed that all persons who contract HIV will eventually develop AIDS. Because of this, we are trying to develop new ways to prevent infection with HIV.
The vaccine that will be tested in this study has been prepared from a small part of the HIV. The part of the HIV used in this vaccine is the "envelope" or coating part of the virus. In this study, researchers will evaluate how well the vaccine is tolerated, how much vaccine should be given, and determine if any side effects occur in response to the vaccination.

Start Date01 Oct 1997

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

100 Clinical Results associated with HIV envelope protein gp120 x gp41

100 Translational Medicine associated with HIV envelope protein gp120 x gp41

0 Patents (Medical) associated with HIV envelope protein gp120 x gp41

Literatures (Medical) associated with HIV envelope protein gp120 x gp41

01 Apr 2016·Journal of VirologyQ2 · MEDICINE

Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop

Q2 · MEDICINE

Article

Author: Bhattacharya, Jayanta ; Murugavel, Kailapuri G. ; Deshpande, Suprit ; Boliar, Saikat ; Shrivastava, Tripti ; Patil, Shilpa ; Koff, Wayne C. ; Kumar, Rajesh ; Chakrabarti, Bimal K. ; Bansal, Manish ; Srikrishnan, Aylur K. ; Samal, Sweety ; Solomon, Suniti ; Goyal, Rajat ; Simek, Melissa ; Chaudhary, Nakul Kumar

ABSTRACTBroadly neutralizing antibodies isolated from infected patients who are elite neutralizers have identified targets on HIV-1 envelope (Env) glycoprotein that are vulnerable to antibody neutralization; however, it is not known whether infection established by the majority of the circulating clade C strains in Indian patients elicit neutralizing antibody responses against any of the known targets. In the present study, we examined the specificity of a broad and potent cross-neutralizing plasma obtained from an Indian elite neutralizer infected with HIV-1 clade C. This plasma neutralized 53/57 (93%) HIV pseudoviruses prepared with Env from distinct HIV clades of different geographical origins. Mapping studies using gp120 core protein, single-residue knockout mutants, and chimeric viruses revealed that G37080 broadly cross-neutralizing (BCN) plasma lacks specificities to the CD4 binding site, gp41 membrane-proximal external region, N160 and N332 glycans, and R166 and K169 in the V1-V3 region and are known predominant targets for BCN antibodies. Depletion of G37080 plasma with soluble trimeric BG505-SOSIP.664 Env (but with neither monomeric gp120 nor clade C membrane-proximal external region peptides) resulted in significant reduction of virus neutralization, suggesting that G37080 BCN antibodies mainly target epitopes on cleaved trimeric Env. Further examination of autologous circulating Envs revealed the association of mutation of residues in the V1 loop that contributed to neutralization resistance. In summary, we report the identification of plasma antibodies from a clade C-infected elite neutralizer that mediate neutralization breadth via epitopes on trimeric gp120 not yet reported and confer autologous neutralization escape via mutation of residues in the V1 loop.IMPORTANCE A preventive vaccine to protect against HIV-1 is urgently needed. HIV-1 envelope glycoproteins are targets of neutralizing antibodies and represent a key component for immunogen design. The mapping of epitopes on viral envelopes vulnerable to immune evasion will aid in defining targets of vaccine immunogens. We identified novel conformational epitopes on the viral envelope targeted by broadly cross-neutralizing antibodies elicited in natural infection in an elite neutralizer infected with HIV-1 clade C. Our data extend our knowledge on neutralizing epitopes associated with virus escape and potentially contribute to immunogen design and antibody-based prophylactic therapy.

16 Jul 2004·Journal of Leukocyte BiologyQ3 · MEDICINE

R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism

Q3 · MEDICINE

Article

Author: Esté, José A ; Blanco, Julià ; Clotet, Bonaventura ; Barretina, Jordi

AbstractThe use of CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5) by X4 and R5 human immunodeficiency virus (HIV) envelopes (Env) influences HIV cytopathicity. Here, we have evaluated the role of CCR5 and gp41 in Env-induced cell death occurring during the contacts of uninfected, primary cells with MOLT cells infected with different R5 and X4 HIV isolates. As reported for X4-Env, R5 HIV-infected cells destroyed CD4 T cells expressing the appropriate coreceptor by inducing the formation of syncytia and the death of single target cells. Therefore, only the small (<10%) CCR5+ subset of primary CD4 T cells was sensitive to cellular presentation of R5-Env, and CCR5–CD4 T cells showed complete resistance to R5-Env-mediated cell death. X4- and R5-infected cells killed single primary cells by a common mechanism that was dependent on gp41 function and induced a rapid loss of mitochondrial membrane potential and plasma membrane integrity in target cells. Single-cell death was not affected by the blockade of HIV replication in target cells or G-protein signaling through CXCR4/CCR5. In contrast, caspase inhibition (Z-Val-Ala-Asp-fluoromethylketone) profoundly changed the outcome of cell-to-cell contacts by reducing the number of single dead CD4 T cells and increasing the rate of syncytium formation. In conclusion, X4 and R5 HIV Env share a common gp41-dependent mechanism to kill CD4 T cells during cellular contacts. Env tropism and coreceptor expression but not differential killing mechanisms seem to govern the extent of cytopathic effects induced by HIV infection.

01 Apr 2004·Drug Resistance UpdatesQ1 · MEDICINE

HIV resistance to the fusion inhibitor enfuvirtide: mechanisms and clinical implications

Q1 · MEDICINE

Article

Author: Daria J Hazuda ; Michael D Miller

The increasing prevalence of HIV isolates resistant to one or multiple antiretroviral drugs has fueled the search for new agents that work by novel mechanisms. Enfuvirtide (ENF), licensed in 2002, is the first marketed antiretroviral (ARV) agent that targets viral entry. ENF blocks the virus replication cycle by binding to gp41, a critical component of the machinery used by HIV to enter host cells. As with all ARVs, HIV can evolve resistance to ENF. However, resistance to ENF appears to be somewhat more complex and can derive through either direct or indirect pathways. Direct resistance occurs when mutations in the first heptad repeat of gp41, which constitutes the ENF-binding site, reduce ENF binding. Indirect resistance is not attributable to changes in the ENF-binding site per se, but rather to changes in the HIV envelope glycoprotein (gp120) that reduce ENF susceptibility by more complex mechanisms. The extensive gp120 amino-acid sequence heterogeneity found in primary viral isolates results in unusually broad variability in susceptibility to ENF, and indeed to other classes of HIV entry inhibitors. Clinical data reported to date do not provide clear evidence that virological outcome of ENF therapy can be predicted by either genotypic or phenotypic analysis of viruses present in patients at initiation of ENF therapy. Although ENF offers an exciting opportunity to treat multi-drug resistant HIV, these observations suggest a greater understanding of ENF resistance may be required to ensure the most effective use of ENF in infected patients. Many aspects of the complexities observed in ENF resistance are likely to be relevant for other classes of HIV entry inhibitors currently in development.

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